BioMG2800
BIOMG 2800 Lecture in Genetics and Genomics
Practice Final Exam
As the name implies, this Practice Exam is an optional exercise for your own preparation. This
Practice Exam is derived from an exam given in a previous semester.
We strongly encourage you to answer the questions as if it was your exam before looking at this
answer key (you lose the "practice" aspect if you only read the answer key).
BioMG2800
Q1. True / False questions. Place your answer (T or F) in the box to the right of each statement.
Recessive mutations always cause the loss of some function. F
The frequency with which a bacterial cell acquires two chromosomal genes
together by taking up DNA from the environment increases as the distance T
between the genes decreases.
RNA interference is an excellent technique to model gain-of-function mutations. F
Homologous chromosomes always have the same alleles. F
Fragments of human genomic DNA cut with MboI ( 5' ^GATC 3') could be inserted
into a plasmid vector cut open with BamH1 (5' G^GATCC 3'). T
In mice, mutation X is a missense mutation at position 21 of the Tir gene and
mutation Y represents a nonsense mutation at position 22 of the same gene. A
mouse heterozygous for mutation X and mutation Y can produce recombinant T
gametes with a wildtype Tir gene.
A CRISPR/Cas9 induced DSB and the non-homologous end joining (NHEJ) repair
pathway can be used to replace a mutant allele with a WT allele. F
Q2. Consider the trihybrid cross: AA BB CrCr X aa bb CRCR
A and B are dominant, CR & Cr are co-dominant. The three genes assort independently. F1
progeny are interbred to produce F2 progeny.
a. How many phenotypic classes do you expect in the F2 progeny?
12
b. What is the probability of the aa bb CRCR genotype in F2? State your answer as a fraction or
the whole numbers 0 or 1.
1/64
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Q3. An SSR locus is PCR amplified from the genome of an XXX female and her two parents. The
PCR products are analyzed on a gel with the following results.
When did non-disjunction occur? Bold or circle the correct answer(s) below.
i. Meiosis I in the father
ii. Meiosis II in the father
iii. In the father during either Meiosis I or Meiosis II
iv. Meiosis I in the mother
v. Meiosis II in the mother
vi. In the mother during either Meiosis I or Meiosis II
vii. During an early division of the zygote
Q4. In cats, there is a gene which produces ticked fur (bands of different colors on each hair)
called Agouti (H). The recessive allele (h) for this gene produces hair that has a solid color from
end to end. In addition, there is a coat color gene which has a recessive albino allele (a) which,
in the homozygote, prevents the production of any coat color pigment, resulting in a white cat,
the traditional albino. Note that the H & A genes are unlinked.
An albino female cat is mated to a solid brown male cat. All of their offspring are Agouti.
The males and females among these offspring are allowed to freely intermate, producing a
flock of F2 kittens. Predict the phenotypic ratio (Agouti, solid brown, white) for fur color among
these many grandkittens.
9 Agouti : 3 Solid Brown : 4 White (Albino)
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Q5. You isolated 5 adenine auxotroph mutants in yeast:
ade1, ade2, ade3, ade4, ade5.
You mated the haploid mutants in all pairwise combinations and tested the resulting diploids
for their ability to grow on medium without adenine. Results are shown below, where “yes”
means that the diploid can grow without adenine and “no” means it cannot.
ade1 ade2 ade3 ade4 ade5
ade1 no no yes yes yes
ade2 no yes yes yes
ade3 no yes no
ade4 no yes
ade5 no
a. Are ade1 and ade2 alleles of the same gene?
yes
b. Are ade1 and ade3 alleles of the same gene?
no
Q6. The sequence of the template strand of the beginning of the coding region of a protein
coding gene:
3’ TACTTGCTG 5’
What are the sequences of the mRNA and amino acids? Use the polarity indicated in the boxes
below.( i.e. 5’ - 3’, N’ - C’). A codon table is provided on the last page of this exam.
Sequence of mRNA 5’ AUG AAC GAC 3’
Sequence of protein. N- M/Met N/Asn D/Asp
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Q7. You are analyzing the following human pedigree.
Assuming complete penetrance, the inheritance of the affect trait in this family is could be
which of the following: Choose all that apply by bolding or circling your answer choice(s).
i. Autosomal dominant
ii. Autosomal recessive
iii. X-linked dominant
iv. X-linked recessive
v. Y-linked
vi. cannot be determined
Q8. The MYC gene is known to be amplified (many extra copies of the chromosome region
encompassing MYC) in some human cancers. You want to engineer a mouse model, to assess
the oncogenic activity of the human MYC gene. Which of the following experiments could serve
this purpose? Bold or circle your answer choice(s) below.
i. A mouse in which the promoter region of the endogenous MYC gene is replaced by a
strong promoter.
ii. A mouse carrying a transgene where a strong promoter drives the human MYC
gene.
iii. A mouse in which the endogenous MYC gene is replaced by the human MYC gene.
iv. A mouse in which the endogenous MYC gene has a nonsense mutation.
v. A mouse carrying many extra copies of the promoter region of the endogenous MYC
gene.
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Q9. The insulin receptor (IR) gene is normally strongly expressed in the intestine and neurons of
C. elegans. To analyze the sequences that regulate its expression, you engineered a number of
constructs as shown below.
The top construct contains the genomic region 5’ to the transcriptional start site of IR, which
when fused to GFP, produces GFP expression in both the intestine and neurons. The various
blue lines below (1-8) indicate sequences corresponding to part of the region and were also
fused to GFP and the resulting GFP signal in C. elegans was assayed and indicated on the left.
a. Based on the diagram provided, indicate which region(s) (A-E) represent:
The basal promoter E
Intestinal-specific enhancer C
Neuronal-specific enhancer B
b. In a next series of experiments, you plan to create a plasmid that can express the IR gene
product with GFP fused (in frame) at the C terminus of IR. In addition to the 5’ regulatory DNA
necessary for gene expression, what additional genetic information will you include? Bold or
circle your answer(s) below.
i. IR coding sequence (including Stop codon)
ii. IR coding sequence (not including Stop codon)
iii. GFP coding sequence (including Stop codon)
iv. GFP coding sequence (not including Stop codon)
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Q10. The pedigree shows a completely penetrant, dominant disease. The alleles for a SNP locus
are shown (A or C). The disease allele is rare and has a single origin in the pedigree.
a. Which of the four matings are informative (can provide information about linkage) given that
the male involved in mating 1 is heterozygous for the disease allele? Bold or circle your answer
choice below.
i. Mating 1, 3
ii. Mating 2, 4
iii. All four mating are non-informative
iv. All four mating are informative
b. Assuming linkage between the disease gene and the SNP locus, what is the genetic distance
between the two loci? Bold or circle your answer choice below.
i. 6.25 m.u.
ii. 7.1 m.u.
iii. 10 m.u.
iv. 14.3 m.u.
v. 20 m.u.
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Q11. A mouse is a heterozygote for an inversion of an autosome. The homologous
chromosomes are sketched below. The brackets [ ] indicate the locations of the inversion
breakpoints. These breakpoints are shown on both homologs for convenience, but of course
only one of the chromosomes contains the inversion while the other has the normal order of
genes. It does not matter which chromosome is which.
From the selections below, choose which unbalanced chromatid(s) could be produced in this
mouse during meiosis. Place your answer(s) in the box below.
a.
b.
c.
d.
e.
f.
Place answer choice(s) here:
d
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Q12.
a. Design two PCR primers, 6 bp long each, that can be used to amplify only the DNA region
highlighted in gray (i.e. produce DNA products that correspond only to the region highlighted in
gray). Bold or circle your answer choice(s) below.
5’ CAAGAATACACGATTCGCAGGACATCGGCGTGACACTGTCCAGGATA 3’
3’ GTTCTTATGTGCTAAGCGTCCTGTAGCCGCACTGTGACAGGTCCTAT 5’
i. 5’ ATTCGC 3’ & 5’ TGACAC 3’
ii. 5’ TAAGCG 3’ & 5’ GTGTCA 3’
iii. 5’ ATTCGC 3’ & 5’ GTGTCA 3’
iv. 5’ TAAGCG 3’ & 5’ TGACAC 3’
v. 5’ TACACG 3’ & 5’ TGGACA 3’
vi. 5’ ATGTGC 3’ & 5’ ACCTGT 3’
vii. 5’ TACACG 3’ & 5’ TGTCCA 3’
viii. 5’ ATGTGC 3’ & 5’ TGGACA 3’
The above map shows a wild-type chromosome (indicated by the thick black line), the
horizontal thin lines show locations of six PCR primers. The full length of the primers must
anneal to target DNA to work for PCR. The two red vertical lines show the position of a deletion
found on other chromosomes.
b. List all primer pairs that will produce a product (of any size) in an individual homozygous WT
(no deletion). Write your answer in the format of 7/8; 9/12; etc. Note that the order of
primers does not matter, for example, 7/8 is the same pair as 8/7. If none will work, write
“none”.
1/3, 2 /3
c. List all primer pairs that will produce a product (of any size) in an individual homozygous for
the deletion. Write your answer in the format of 7/8; 9/12; etc. Note that the order of primers
does not matter, for example, 7/8 is the same pair as 8/7. If none will work, write “none”.
none
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Q13. In 1950, a ship landed on a tropical island with no endemic mammals. A few rats escaped
the ship and quickly populated the island. They remained an isolated population until the island
was revisited in 2021. Scientists discovered that the island rats were all significantly smaller
than wild type (WT) rats, so they brought some back to a laboratory for a genetic investigation.
For 5 SNPs on chromosome 1, WT rats have ONLY 8 haplotypes (no others have ever been
discovered). They are (... indicates intervening DNA sequence):
1) A..A..T..G..C 5) A..A..T..G..T
2) T..C..G..C..T 6) T..C..G..C..C
3) A..A..G..C..T 7) A..A..G..C..C
4) T..C..T..G..C 8) T..C..T..G..T
Note that SNP1 is the leftmost and SNP5 is the rightmost in each haplotype.
a. If you genotype WT rats, what are all possible genotypes you could get for SNP1? (Write
your answer as A/T, G/C, etc.)
A/A, A/T, and T/T
b. Based on the above haplotypes, place a line (|) between the SNPs where the recombination
hotspots are. (It is simplest to use the lower-case letter l for this purpose)
for example: SNP# | SNP#
SNP1 SNP2 SNP3 SNP4 SNP5
SNP1 SNP2 | SNP3 SNP4 | SNP5
c. You next genotype the island rat population and discover that they ONLY have haplotypes 2
and 6! For an island rat, what are all possible genotype(s) you could get for SNP1?
T/T only
d. True or false, if recombination happened in an island rat, a new haplotype regarding the 5
SNPs could be created.
FALSE. There is only 1 polymorphic SNP (SNP5) in the island rats. Therefore, recombination
would not create a new haplotype. Only mutation could.
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You next genotype WT and island rats on a standard genotyping array that includes SNP1-5
from the haplotype. You then perform a genome-wide association study (GWAS) to help
determine why island rats are so small. Below are the results with SNPs1-5 in blue and the
other genotyped SNPs in grey. The corrected p-value threshold is the dotted line.
e. What allele at SNP3 would be associated with small body size?
f. What SNP(s) are significantly associated with small body size?
SNP3 & SNP4
g. Notably, WT rats with haplotypes 2 and 6 are NOT any smaller than WT rats with other
haplotypes. Knowing this, explain IN ONE SENTENCE what you predict is the genetic cause of
small body size in the island rats and where it could be located in the rat genome?
Small body size might be caused by a mutation somewhere in the
linkage block that includes SNP3 and SNP4.
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Q14. An orphan strikes it rich playing Powerball. Within days, three burly men show up, each
claiming to be her long-lost but devoted father. As the resident geneticist, you obtain DNA
samples from all four people involved and look at their profile for three different polymorphic
SSR (Simple Sequence Repeat) loci. These loci are polymorphic for repeats of CA, for example
(CA)18, indicates the nucleotides CA are repeated 18 times.
The results from the tests (PCR products separated by gel electrophoresis) are shown:
Allele frequencies in the population:
Locus 1 Locus 2 Locus 3
(CA)18 = 0.19 (CA)22 = 0.4 (CA)16 = 0.03
(CA)22 = 0.01 (CA)25 = 0.2 (CA)18 = 0.2
(CA)28 = 0.6 (CA)28 = 0.02 (CA)22 = 0.25
(CA)32 = 0.2 (CA)32 = 0.2 (CA)28 = 0.17
(CA)36 = 0.18 (CA)36 = 0.35
Based on these results and the allele frequencies,
a. Which candidate can you conclusively rule out as the possible father?
3 (d)
b. Which candidate are you more inclined to believe to be the possible father?
Is this a firm conclusion? Explain your answer IN ONE SENTENCE.
1 (b) No, since the frequency of the 3 alleles are low in the population, the
probability of a match by chance is low.
c. Based on the information provided, indicate the possible alleles for loci 1, 2, 3, for the
orphan’s mother.
Locus 1 Locus 2 Locus 3
(CA)____28____ (CA)___ 25___ (CA)___ 36___
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Q15. Scientists treated wildtype mice with X-rays, and they found among the progeny a mouse
(I-1 in the pedigree below) carrying a deletion of the region corresponding to the one missing in
many human patients with Angelman syndrome or Prader-Willi syndrome. This mouse was
normal in appearance and fertile, but she suffered from seizures; this syndrome is indicated
with blue symbols below.
Several generations of mating resulted in the pedigree that follows. Interestingly, some
mice showed a completely different mutant phenotype: these animals survived only one week
because they had difficulties in respiration. This syndrome is indicated by red symbols with a
slash.
a. In humans, the gene responsible for Prader-Willi syndrome is maternally imprinted, while the
gene responsible for Angelman syndrome is paternally imprinted. Which mouse syndrome
(blue or red) would be a model for Prader-Willi syndrome? Bold your answer below.
Red Blue
b. Was the mouse treated with X-rays (the parent of I-1) a male or a female? Bold your answer
choice below.
Male Female
c. If IV-1 is mated with a wild-type male, what is the probability that a male offspring of this
mating will have the blue syndrome? What is the probability that a female offspring of this
mating will have the blue syndrome? State your answers as a fraction or the whole numbers 0
or 1.
Male offspring will have the blue syndrome? 1/2
Female offspring will have the blue syndrome? 1/2
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d. Mice with the red syndrome die too early to mate. But suppose (for the sake of argument)
that they survived long enough to mate. Which one of the following statements likely would be
true if the mouse with the red syndrome was a female? Bold or circle your answer choice(s)
below.
i. All of her progeny would have the red syndrome.
ii. Approximately half of her progeny would have the red syndrome.
iii. All of her progeny would have the blue syndrome.
iv. Approximately half of her progeny would have the blue syndrome.
v. Approximately half of her progeny would have the red syndrome and the other half
would have the blue syndrome.
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Q16. A mouse model carrying a mutation in the abc tumor suppressor gene has been
engineered to model cancer progression. The mutation in abc is shown in red below.
a. The homozygous abc mutant mice developed liver cancer with 100% penetrance by 6
months of age. The heterozgyous abc mutant also succumbed to liver cancer, but not until ~18
months of age. In 1-2 concise sentences, explain the likely cause of these observations.
After some time, the wt allele in the heterozygotes will become mutated and animals will
develop tumors.
b. You decided to try a CRISPR-Cas9 strategy to reverse the mutation and monitor for cancer
development in the mouse model. You microinject a mixture of the sgRNA, the repair template,
and Cas9 mRNA into one-cell embryos of the homozygous abc mutant mice. The embryos were
then transferred into surrogate females and allowed to develop fully. Once the mice were born,
they were genotyped to assess for correct editing.
Choose the guide sequence (i.e. the target sequence that the sgRNA would look like) for
this strategy. Recall gRNA helps locate Cas9 to the correct target region through base-pairing,
and Cas9 cuts near the PAM site. Bold or circle your answer.
i. 5’ TCT TTG AAA GAG CAA CAA AA 3’
ii. 5’ TCT TTG AAA GAG CAA TAA AA 3’
iii. 5’ TTG AAA GAG CAA CAA AAT GG 3’
iv. 5’ AGA AAC TTT CTC GTT ATT TT 3’
v. 5’ TCT TTG AAA GAG CAA TAA AAT GG 3’
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For your convenience the figure from the previous page is shown again here:
c. You want to design the repair template so that: (i) it corrects the mutated sequence to
encode a wild-type ABC gene product, and (ii) it enables genotyping for the correctly edited
mice without having to sequence the abc gene by virtue of a restriction enzyme recognition site
for the enzyme TseI that will be present in repaired alleles but not in mutant alleles. (The
recognition site for TseI is G^CWGC, where W is A or T.)
Choose the one best repair template design from the list below. In each of the choices, the
dots at the beginning and end are nucleotides from the abc gene to allow for homologous
recombination. For your convenience, the first choice in the list is the wild type allele
of abc. There is a codon table on the last page of this exam.
i. 5’ …AGT TCT TTG AAA GAG CAA CAA AAT GGC TTC AAC…3’(WT)
ii. 5’ …AGT TCT TTG AAA GAG CAG CAA AAT GGC TTC AAC…3’
iii. 5’ …AGC TGC TTG AAA GAG CAA TAA AAT GGC TTC AAC…3’
iv. 5’ …AGT TCT TTG AAA GAG CAA TAA AAT GGC TGC AAC…3’
v. 5’ …AGC TGC TTG AAA GAG CAA CAA AAT GGC TTC AAC…3’
d. You identified 10 mice with the editing you intended. None of the mice showed 100%
editing. Instead, they had the correct editing ranging from 30-60%. Choose all the statements
that apply to this observation by bolding or circling your choice(s).
i. The editing is not 100% efficient. Some editing happens after multiple rounds of cell
division, so the animal is essentially a mosaic with edited and mutant abc genes.
ii. Since the microinjection was done in one-cell embryos, the editing should occur 100% in
the zygote and, upon cell divisions, all cells of the animal would have the edited mdx
gene. However, the edited sequence is not stable, and can revert back to the mutant
sequence.
iii. Since the editing could only occur in the somatic cells of the animal, the germline cells
would continue to harbor the mutated abc gene.
iv. After Cas9 induces the DNA cut, cells will usually use the homologous chromosome,
which carries the mutation, as the repair template. That is why the repair % usually did
not exceed 50%.
v. The editing process sometimes only affects one of the two gene copies; thus the edited
sequence would never exceed 50%.
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e. You monitored the phenotype of the edited mice and observed that they nevertheless
started to develop tumors at 10-18 months of age, in contrast with at 6 months of age in the
unedited homozygote.
Explain, in one concise, sentence why even though you achieved correct editing in these mice,
the editing process did not substantially alleviate cancer progression. In a second concise
sentence, explain why various edited mice developed cancer at different times (between 10-18
months). Your explanations should focus on the abc gene.
The unedited cells carry the abc mutation and will become cancerous and grow out into
tumors.
The variable time elapsed reflected that 40-70% of the cells were NOT edited, so remained
homozygous, and they will accumulate additional mutations and eventually gained growth
advantage and grow out into a tumor.
