Name______KEY________________________

SID_____________________

MCB104 1st midterm

Spring, 2015

Before you start, print your name and student identification number (S.I.D) at
the top of each page. There are 11 pages including this page.
You will have two hours for the 100-point exam.
Place your answer on the front of the page. Only answers in that space will be
graded.
You may write in pencil; however, to preserve your rights to a regrading, you must
write your answers in pen.
Good luck!

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This section is for grading. Do not write here.
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EXAM SCORE: __________

Name______KEY________________________

SID_____________________

1. (9 points). A mutation results in recessive obesity. Heterozygous individuals are of

normal weight. A woman homozygous for this mutation is obese and wants to have
children with a man that does not have the mutation. What is the probability that her
children with this man will be obese? Explain your reasoning for each answer.
a) If the mutated gene is X linked (3 points)
All of the daughters will be of normal weight because they will be
heterozygous, and half of the sons will be obese because the have a 50%
chance of inheriting the X with the mutation.

b) If the mutated gene is maternally imprinted (3 points)

All of the children will be of normal weight since they will be heterozygous and
inherit an active gene from their father.

c) If the mutated gene is paternally imprinted (3 points)

Half of the children will be obese. Those that inherit the wild-type allele from
their mom will be normal, but those that inherit the mutant allele from mom
and a silenced gene from dad produce no functional products for the gene.

Responses below this line will not be graded

Name______KEY________________________

SID_____________________

2. (20 points) You cross female flies that appear wild type to males that have
lozenge-shaped eyes and small wings. The number of progeny for each phenotypic
class is shown below.
Phenotype
Lozenge eyes
Small wings
Normal eyes and wings
Lozenge eyes and small wings

# progeny
445
455
47
53

a) The parents of the phenotypically wild-type females (i.e., the females that you
crossed to the mutant males) came from pure breeding stocks. What were the eye
and wing phenotypes of these females parents? (4 points)
One parent had lozenge eyes (and normal wings) and the other had small
wings (and normal eyes). Parenthetical phenotypes not necessary.

b) What is the distance in map units between the lozenge (lo) and small wing (sw)
genes. (4 points)
47 + 53 /1000 = 0.10 x 100% = 10 map units

Responses below this line will not be graded

Name______KEY________________________

SID_____________________

c) You cross the lozenge-eyed and small-winged female progeny to the wild-type
males and find that all the females appear wild type and all the males have lozenge
eyes and small wings. What can you say about the lo and sw genes. (4 points)

They are on the X chromosome.

d) After looking through many more progeny from the cross described in c), you find
a female with lozenge eyes and small wings and a male that appears wild type.
What are the karyotypes of these two animals? (4 points)
The female is XXY and the male is X0.

e) Describe the events that produced these progeny (female with lozenge eyes and
small wings and the wild-type male) and the source of each of their sex
chromosomes. (4 points)
Nondisjunction in meiosis I or II in the female parent. Female progeny
inherited two X chromosomes from their mother and Y from their father. Male
progeny inherited their single chromosome from their father.

Responses below this line will not be graded

Name______KEY________________________

SID_____________________

3. (11 points) Male kangaroos are marsupials, and as with placental mammals,
marsupial males are XY and females are XX. You are interested in asking whether
dosage compensation in marsupials is the same as in placental mammals by
studying kangaroos. You get permission from the local zoo to collect blood from two
kangaroo parents, and their two female offspring and two male offspring. You take
the blood back to the lab and look for X chromosome polymorphisms that differ
between the male and female parents. PCR amplification and sequencing shows
different sequences in the coding sequences of two genes that you call A and B. The
female parent is polymorphic for gene A, and you label her two alleles A-1 and A-2.
The male parent has yet a different allele that you label A-3. For the B gene, the
female parents two chromosomes have the same allele that you label B-1 and the
male parent has a different allele that you label B-2. The two female progeny are A1/A-3; B-1/B-2 and A-2/A-3; B-1/B-2, and the male progeny are both A-1; B-1.
a) Why are these results consistent with both the A and B genes being X-linked? (3
points)
The female offspring inherit alleles from both parents, but the male offspring
inherit their single allele from their mother
b) You now extract RNA from the remainder of the blood samples, generate cDNAs
from mRNA, amplify by PCR the cDNAs from the two genes that contain the
polymorphisms, and sequence the DNA. As expected, you find that both male
progeny express the A-1 and B-1 alleles. The results from the female progeny are
interesting. In the A-1/A-3; B-1/B-2 female, only the A-1 and B-1 alleles are
expressed. In the A-2/A-3; B-1/B-2 female, only the A-2 and B-1 alleles are
expressed. This is not a sampling error, since you repeat the experiment from
several other tissue sources and get the same result. Subsequent studies show that
this pattern of gene expression holds for all X-linked genes analyzed. From these
findings, which aspects of mammalian and kangaroo dosage compensation are
similar and which are different. Explain your reasoning. (8 points)
Kangaroo and mammalian dosage compensation both involve X inactivation
because only one gene from the two X chromosomes are expressed. (4 points)
Only the maternal X chromosome is expressed in female kangaroos indicating
that only the paternal X is inactivated. In mammals X inactivation is random,
with some cells expressing the maternal X and others expressing the paternal
X. (4 points)

Name______KEY________________________

SID_____________________

4. (16 points) The transcription factor Pointed is required for R7 development. This
was shown using a trick that we did not discuss in class. Investigators started with
animals that are heterozygous for a loss-of-function allele of pointed and made
clones of cells in the eye that are homozygous for the pointed mutant allele. The
ommatidia (repeating eye units that contain the eight photoreceptor cells, four cone
cells and other support cells) in these homozygous mutant clones lack the R7 cell,
where the surrounding ommatidia that are heterozygous for the pointed mutation
have R7.
a) Why do you think that the investigators had to use this trick of generating clones
of homozygous mutant eye tissue in heterozygous animals instead of simply
analyzing animals that are homozygous for the mutant allele of pointed? (4 points)
The trick was used because the homozygous mutant animals die before
reaching adulthood.

b) Upon activation of Ras by Sev, MAP kinase (MAPK) is activated and enters the
nucleus where it phosphorylates transcription factors involved in R7 development. A
mutation known as sevenmaker results in extra R7 cells in heterozygous animals
and is an allele of the MAPK gene. From what you now know about how MAPK acts
in Sevenless signaling, what type of allele is sevenmaker? (4 points)
It is a gain of function. Credit for hypermorphic or neomorphic.

Responses below this line will not be graded

Name______KEY________________________

SID_____________________

c) The investigators reasoned that as a transcription factor, Pointed could either

function upstream MAPK (for example, Pointed could be required for the
transcription of the MAPK gene) or it could function downstream of MAPK (for
example, MAPK could phosphorylate and activate Pointed). How did the
investigators distinguish between these two possibilities? Just describe the
genotypes and phenotypes of the animals that they analyzed. (4 points)
They generated homozygous mutant pointed clones in sevenmaker/+ animals
and scored the number of R7 cells in the clones.

d) What was the result of the investigators experiment that showed that MAPK acts
upstream of Pointed to promote R7 development? (4 points)

The ommatidia in the clone lack R7 cells.

Responses below this line will not be graded

Name______KEY________________________

SID_____________________

5. (10 points) Below is a pedigree for a rare human disease. Squares represent
males, circles females, and the filled circles and squares exhibit the disease
phenotype.

a) You first suspect that it is a paternally imprinted disease trait. What makes this
unlikely? (3 points)

All of the affected mothers progeny are affected.

b) What is the pattern of inheritance? (3 points)

Maternal

c) The trait exhibits variable expressivity. What is the likely cause of this variability
that is specific to this type of inheritance? (4 points)

Variability in heteroplasmy. Or different mutant : wild-type mtDNAs.

Name______KEY________________________

SID_____________________

6. (15 points) You decide to make a mutant mouse that is defective for Your Favorite
Gene (YFG) using CRISPR.
a) Besides a construct that will express a CRISPR sgRNA, what else will you
express in the embryonic stem (ES) cells? (3 points)
Cas9
b) CRISPR is very efficient, and you find several ES clones that have small deletions
and/or insertions. What is the name of the repair mechanism that generated these
mutations? (3 points)
Nonhomologous end joining or NHEJ
c) After sequencing the DNA of YFG from these clones you find several clones that
have the type of deletion in that you are interested in using. How will these deletions
affect the expression of the gene? (3 points)
Genes that cause a frameshift of the reading frame.
d) You inject these cells into the blastocysts from a mouse of a different origin.
Besides the difference in YFG, what difference between the ES cells of the
blastocyst and the injected ES cells allows you to identify the chimeric offspring? (3
points)
The injected ES cells are homozygous for a dominant coat color marker and
the ES cells of the blastocyst are homozygous for the recessive marker.
e) When crossing the chimeric male mice to female mice. What types of progeny are
you looking for? (3 points)
Mice that have the dominant coat color phenotype and contain the mutated
gene.

Name______KEY________________________

SID_____________________

7. (13 points) You cross a five Drosophila mutants that have a recessive abnormal
bristle (ab1-ab5) phenotype to each other and get the results below.

ab1
female
parent

ab2

ab1

ab2

+
-

Male parent
ab3

ab3
ab4

ab4

ab5

ab5

- indicates failure to complement, + indicates complementation

a) How many complementation groups do these mutations define? Which alleles
belong to each complementation group? (3 points)
Four complementation groups (2 points). ab2 and ab3 are in the same
complementation group and ab1, ab4 and ab5 all define their own
complementation group (2 points).
2) You cross two strains that are heterozygous for different deficiencies (deletions)
as males to each of the females that are homozygous for each of the mutations that
cause the abnormal bristle phenotype. The cross with Df1/+ males generates
progeny with abnormal bristles with the ab2, ab3 and ab5 strains but only normal
bristles with the ab1 and ab4 strains. The cross with Df2/+ males generates progeny
with abnormal bristles with the ab2, ab3 and ab1 strains but only normal bristles with
the ab4 and ab5 strains. What can you say about the positions of the genes defined
by these mutations? (4 points)
The genes defined by ab1, (ab2, ab3) and ab5 are linked (1 points). They are in
the order ab1, (ab2, ab3), ab5. (2 points) Cant say anything about ab4. (1
point)

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Name______KEY________________________

SID_____________________

c) The phenotype of the ab5/Df1 animals has a more severe bristle phenotype than
the ab5/ab5 animals. What can you say about the ab5 mutation? Explain your
reasoning. (3 points)
It is a partial loss of function mutation or a hypomorphic mutation.

d) You identify the gene defined by the ab5 mutation and sequence the mutant
gene. You find that the mutation is a point mutation in the fourth codon of the
reading frame. What type of point mutation is ab5? Explain your reasoning. (3
points)
A missense mutation

8. (6 points) In the human genome, there are many more copies of retrotransposons
(these move though an RNA intermediate) than DNA transposable elements.
a) Why? (3 points)

When retrotransposons move, they leave a copy behind. DNA transposable

elements do not.
b) Why do individuals with defects in nucleotide excision repair have problems with
skin cancer? (3 points)
They cannot remove the DNA damage caused by UV.

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