Name:

NOTE THIS IS A PROVISIONAL KEY-

THERE WILL BE ADDITIONAL ANSWER THAT WILL MERIT PARTIAL AND FULL CREDIT.
THE KEY WILL BE UDATED AS THE DR. SHINSKY AND DR BRADBURY GO THROUGH
YOUR EXAMS.

ALSO NOTE THAT YOU WILL NEVER RECEIVE NET NEGATIVE POINTS FOR ANY OF
THE MULTIPLE-CHOICE QUESTIONS.

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Directions:
• There are 13 pages to this exam. This includes Bayes theorem at the end of the exam (page 11). Make
sure your exam is complete. You may remove pages 11-13 from the exam, if you want to use these as
scrap paper.

• Please sign the honor pledge below. If you do not sign the honor pledge your exam will not be
graded.

• You will have 75 minutes to complete this exam.

• Do not write on the back of the exams. Answers written on the back of pages will not be graded!

• All answers must be provided in the space allotted following each question. the blank pages as scrap
paper, however these pages will not be reviewed during grading.

• Multiple choice questions may have more than 1 correct answer.

Choose all correct answers for full credit. Please be short and concise with your short answer questions.
Full credit will be awarded for correct answers that are not otherwise diluted with extraneous or
erroneous information.

• Write your answers in PEN. Exams completed in pencil will not be considered for regrade.

By signing my name below, I pledge my honor that I have

upheld the Code of Academic Integrity of
the University of Pennsylvania in completing this
examination.

Signature: __________________________________

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1) Which of the following explain Mendel’s law of independent assortment (3 pt)?

a) Homologous chromosomes line up randomly during meiosis II (-3)

b) Homologous chromosomes line up randomly during meiosis I (+3)
c) Sister chromatids separate during meiosis II (-3)
d) Sister chromatids separate during meiosis I (-3)
e) None of the above (-3).

2) The finding that parental traits reappear unchanged in the F2 discredited which 2 theories of
inheritance discussed during lecture? Please name them below (2 pt):

____uniparental (preformationist also okay)______ and _________blending__________

3) A mutation has been found within the promoter region of the white gene that encodes an enzyme
required for the production of violet pigmentation in peas. As a result, of a single nucleotide change in the
promoter of white, RNA polymerase II cannot bind the promoter as efficiently as normal. Which of the
following would likely describe the resultant mutant (3 pt)?

a) Hypomorphs (+3)
b) Hypermorphs (-3)
c) Neomorphs (-3)
d) Antimorphs (-3)
e) Amorphs (+0)

4) Hypokalemic Periodic Paralysis is a dominantly inherited disorder associated with mutations in

CACNA1S. In unaffected individuals, CACNA1S forms voltage-dependent calcium channels that
regulate the uptake of calcium into muscle cells. In individuals with Hypokalemic Periodic Paralysis, the
mutated CACNA1S protein interferes with the wild-type CACNA1S protein causing episodic weakness
and paralytic attacks in affected individuals. This mutation is an example of a/an (3 pt)

a) Hypomorph (-3)
b) Hypermorph (-3)
c) Amorph (-3)
d) Neomorph (-3)
e) Antimorph (+3)

5) When studying epistatic relationships, it is very important to use ____________ mutations, whereas
when studying modifier mutations (suppressors and enhancers) it is often more useful to use
____________ mutations (2 pt).

a) amorphic; neomorphic (-2)

b) hypomorphic; amorphic (-2)
c) neomorphic; hypomorphic (-2)
d) amorphic; hypomorphic (+2)
e) hypermorphic; hypomorphic (-2)

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I
1 2 3 4

II
1 2 3 4 5 6 7 8

III
1 2 3 4

IV
1 2 3 4

6) The pedigree above shows the inheritance of hereditary haemochromatosis, which is caused by
relatively common mutations in a haplosufficient locus, HFE. Individuals with haemochromatosis have
increased intestinal absorption of iron, which leads to over-accumulation of iron in various tissues of the
body.
a) What is the most-likely mode of inheritance (4 pt)?

• Autosomal recessive (+4)

• Sex linked recessive (+3) this would make the penetrance in generation II 75% (¾) and in generation IV
0%, which would be odd, but the numbers of individuals are small.
• Autosomal dominant (+3)

b) Considering only individuals 1-5 in generation II, what is the penetrance of this trait (4 pt)?

3/5 or 60% or for autosomal recessive. (+4) If just says incomplete (+1)
Answer should be 75% if they answered Sex linked recessive above (+4) Award +3 for 60%)
Answer should be unknown – unable to determine (+4) If says complete (+2).

AB B
I

II
A A AB BB
1 2 3 4
III
1

7) The pedigree above shows the inheritance of Hunter syndrome along with markers that show 100%
linkage to the IDS2 gene. Based upon this pedigree, you can conclude (circle all correct answers) (4 pt):

a) Individual II-1 is a carrier. (-2) (is affected)

b) Individual II-3 is a carrier (+2)
c) If individual II-2 had a daughter the probability that she would be a carrier is 100% (+2)
d) If individual II-4 had a daughter the probability that she would be a carrier is 50%(-2)
e) If individual III-1 inherits the B allele from his mother, the probability he will be affected is
50%. (-2)
The A marker is linked to the disease. Males who inherit the A are affected, females are carriers. Affected male will
pass the mutant allele onto all of their daughters. For d and e above the probability of carrier or affected is 0%

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8) Beta thalassemia is a blood disorder resulting from mutations of the HBB gene, which codes for beta-
globin, an essential component of adult hemoglobin. Individuals who are heterozygous for amorphic
alleles of HBB (βº/β+) produce sufficient levels of hemoglobin, and have increased resistance to malaria.
The increased resistance to malaria may explain why about 16% of individuals in ancient Greece (where
malaria is still prevalent) were carriers. Homozygosity for the null allele (genotype βº/βº) results in beta
thalassemia. Prior to the development of blood transfusions, individuals with beta thalassemia would not
survive into adulthood. If Zeus, who was a malaria-resistant male in ancient Greece fathered 50 children
with adult women in ancient Greece, what percentage of them would be affected by beta thalassemia (4
pt)?

a) 4% (+4) βº/β+ crossed to female who has a 16% p βº/β+

b) 8% (-4)
c) 16% (-4) (1/2) get the βº allele from Zeus. (1/2) (.16) get the βº from
d) 32% (-4) Zeus’ partners.
e) 50% (-4)

9) The ability to roll your tongue is a dominantly inherited trait. Tongue rollers are R/R or R/r. In
European populations, approximately, 75% of people can role their tongue. Assuming Hardy Weinberg
equilibrium, which of the following statements are correct (4 pt)?
75% rollers 25% non-rollers means
frequency q2 is .25, freq q=0.5; freq
a) The frequency of the r- allele in the population is 25%. (-2) p=0.5 R=0.5 r=0.5
b) The frequency of the R- allele in the population is 75%. (-2)
c) The frequency of the Rr genotype in the population is 25% (-2) In HW equilibrium with 75% rollers
d) 1 in 3 tongue rollers is homozygous for the R allele. (+2) 25% RR +50% Rr =75% thus 1/3 of
e) The frequency of the r- allele in the population is 50%.(+2) rollers are RR

10) If a tongue roller and a non-tongue roller had a child, what proportion of their children would be
tongue rollers (4 pt)?

a) all of them would be tongue rollers (-4)
b) 1/3 would be tongue rollers (-4)
c) 1/2 would be tongue rollers (-4)
d) 2/3 would be tongue rollers (+4)
e) 3/4 would be tongue rollers (-4)
If their answer is this award +2:
In HW equilibrium with 75% rollers
25% RR +50% Rr =75% thus 1/3 of
rollers are RR
Cross R_ to rr. Only rr will be non-
rollers. 1- non-roller = freq rollers.
Thus, freq rr = freq Rr (2/3) prob
passing on r (1/2) = 1/3 are non-
rollers. Rollers are 1-1/3 = 2/3

a) all of them would be tongue rollers

b) 1/3 would be tongue rollers
c) 1/2 would be tongue rollers
d) 2/3 would be tongue rollers
e) 3/4 would be tongue rollers

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11) On a rabbit ranch in Nevada, a mutation arose that gave a “platinum” coat color. The platinum color
proved very popular with rabbit breeders, but the breeders could not develop a pure-breeding platinum
strain. Every time two platinum rabbits were crossed, some normal brown rabbits appeared in the
progeny. For example, the repeated matings of the same pair of platinum rabbits produced 82 platinum
and 38 brown progeny. All other such matings gave similar progeny ratios. Which of the following could
explain these results (4 pt)?

a) the platinum coat color is the result of mutations in two different unlinked genes (-4)
b) homozygosity for the platinum allele results in synthetic lethality (-4)
c) platinum is an epi-allele that produces platinum coat color when hypo-methylated and brown
coat color when fully methylated (-2)
d) homozygosity for the platinum allele results in recessive lethality (+4)
e) homozygosity for the brown allele results in recessive lethality (-2)

12) The axin (axis inhibition) gene in mice encodes a protein that is involved in axis formation in the
mouse embryo. The murine fused allele, AxinFu is a neomorphic version of axin that results in the
development of mice with kinked tail. Inbred mice heterozygous for AxinFu exhibit incomplete penetrance
with an array of tail phenotypes, ranging from kinked tails of varying degrees (variable expressivity) to a
normal tail (indistinguishable from wild-type). Both the penetrance and expressivity of the AxinFu
phenotype depend upon the conditions under which the mice are raised. Based upon what you know about
the regulation of gene expression, what most likely affects the penetrance and expressivity of the AxinFu
phenotype (4 pt).

The AxinFu is an epiallele similar to the Avy allele. The methylation (or epigenetic) state of the AxinFu
allele affects its expression and therefore the phenotype of the mice. Since we are told this is a
neomorphic mutation, as opposed to a loss of function the most likely scenario is that when AxinFu is
hypomethylated (i.e. when the allele is expressed) the mice have kinked tails. When the gene is turned off
by increased methylation or (decreased histone acetylation perhaps) the mice are now show a wild-type
unkinked tail phenotype – this then decreases the penetrance of the trait.

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13) Myotonic Dystrophy (DM) is one of the most common forms of dominantly inherited muscle disease
with an incidence of 1 in 20,000 (affected individuals). The disease is caused by expansion of a CTG
repeat region.

Description CTG repeat size

Normal range 5 to 37
Premutation range 38 to 49
(No symptoms, but children at risk)
Mild 50 to about 150
Classical About 100 to 1000-1500

Congenital About 1000 and greater

A woman with mild Myotonic Dystrophy decides to use polar body testing to choose oocytes that lack the
expanded repeat allele. She takes medication that induces superovulation; 5 secondary oocytes are
harvested and mixed with her partner’s sperm. The results of polar body testing are shown below. The
numbers indicate the length of the CTG repeat region found. a) Clearly circle below, just the oocytes that
would produce unaffected eggs (4 pt).

Oocytes 1 and 4 are good (+2 for oocyte 1; +2 for oocyte 4)(-2 each for oocyte 2, 3 or 5)

Oocyte 1 Oocyte 2 Oocyte 3 Oocyte 4 Oocyte 5

PB1 27/125 27/125 27 125 125

PB2 125 27 125 27 125/27

b) Indicate in no more than one sentence what happened to oocyte 5 (3 pt).

In oocyte 5 there was nondisjunction during meiosis II

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14) The pathway to the right shows the (simplified) pathway for the Chorismate
biosynthesis of tryptophan from chroismate. You have done a screen for
auxotrophic mutants in yeast that can’t grow on media lacking tryptophan. TRP2
Through this screen, you have identified 3 alleles each of TRP2, TRP4 and
TRP1. Unfortunately, you have not identified any alleles of TRP3 or TRP5. You
set up to do another screen to identity mutations in TRP3 or TRP5, but don’t Anthranilate
want any new alleles of TRP2, TRP4 or TRP1.
TRP4
a) What compound/s could you add to your media to avoid isolating new alleles
of TRP2, TRP4 and TRP1 (4 pt)?
PRA

TRP1
if CdRP only +4
if chorismate, anthranilate PRA, and CdRP +2
CdRP

b) You perform the screen and isolate 4 lines that can’t grow on the TRP3
supplemented media (from part a) that lacks tryptophan. You call these 4 lines
tryptophan deficient (wd) 1-4. Complementation tests with these lines give the
following results (- indicates no growth; + indicates growth; wt is wild-type). Indole 3-glycerol phosphate
How many different genes were identified in this screen (4 pt)? 1
TRP5

wd1 wd2 wd3 wd4

Tryptophan
wd1 -
wd2 - -
wd3 - - -
wd4 - - - -
wt + + + +

c) How could you distinguish whether the lines in part b represent mutations in TRP3 or TRP5? Be sure
to indicate your expected results (4 pt).

Prepare media with added indole 3 glycerol phosphate. If the mutants grow they are trp3 alleles. If they
don’t they are likely trp5 alleles and would only grow on media with tryptophan.

If the answer includes the addition of any of the earlier intermediate compounds like CdRP in addition to
indole 3 glycerol phosphate and is otherwise correct +3

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15) In a hypothetical plant, the b gene encodes an enzyme that makes a blue pigment; b+_plants have blue
flowers while b0/b0 (homozygous nulls) plants have white flowers. The transcription of the b gene is
regulated by the t gene; t+_plants transcribe the b gene at levels sufficient to produce wild-type blue
flowers, while t0/t0 (homozygous nulls) plants do not transcribe b. The genes are not linked.

a) If you crossed dihybrid b+/b0; t+/to plant to each other, what phenotypes would be present in the F2
generation and in what ratios (3 pt)?

9 blue to 7 white (+3)

You may also get answers like 9 blue 3 white, 3white, 1 white – Or 9 blue:4 white :3 white (+2)

b) Based soley upon the F2 results could you deduce the order to the b and t genes in the pathway (3pt)?
Why/why not?

No, Because all single and double mutants have the same phenotype you can’t resolve the order without
additional experiments.

c) Plants that are homozygous for a hypomorphic allele of b (bh), have pale blue flowers. Based upon
what you have learned about genetics circle all of statements below that are likely to be true and correct
all of the false statement (10 pt). +2 each –there will be some variation for the corrected false answers –
just make sure that the changes make the statements true.

True 1) Plants that are hemizygous for the bh allele produce less blue pigment than plants
homozygous for bh

2) Hypermorphic alleles of t+ would enhance (suppress) the bh/bh phenotype.

3) Hypomorphic alleles of t+ would enhance (be masked) the b0/b0 phenotype.

4) Plants of the genotype t0/t0; bh/bh would produce very pale blue (white) flowers.

True 5) Plant hemizygous for bh should have the same phenotype as plants with the genotype
h 0
b /b

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A1 10cM briD* 20cM B4 A3 10cM + 20cM B3

A2 10cM + 20cM B6 X A2 10cM + 20cM B5

A1 ? B4

A3 + B5

16) The diagram above shows a cross between a male fly with a dominant allele of the bristled gene
(briD*) to a wildtype male. The bristled gene sits in between two polymorphic markers A and B. As
shown in the diagram of the relevant chromosome, the bristled gene is 10 cM from marker A and 20 cM
from marker B. Given that an F1 fly has inherited both the A1 and B4 markers from the affected female
parent, what is the probability it has also inherited the briD* allele? If you are unsure of your answer, draw
out the all of the possible gametes that the female fly produces and calculate their percentage (8 pt).

a) 98%
b) 72%
c) 74%
d) 2%
e) 97% (+4 if any other answers are selected +0)

Please award +4 points if all of the possible gametes and their proportions are correct but the circled
answer is not.

A1-- *-- B4 = .36

A2-- +-- B6 = .36

A1--+--B6 = .04 A1-- *-- B4 .36/(.36+.01)

A2--* --B4 = .04

A1-- *-- B6 = .09

A2-- +-- B4 =.09

A1--+--B4 = .01
A2--*--B6 = .01

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