Biol 321 Spring 2013 Final Exam Study Sheet
Comments on final exam: By necessity the final exam is cumulative in the sense that much of
the material that was covered earlier in the course is directly relevant to material we have
discussed recently (ie. Linkage, meiosis and crossing over; mutations and cancer genetics and so
forth).
• The final exam is worth 90 pts. and will undoubtedly include questions testing your
understanding of cancer genetics, DNA profiling, direct detection of genotype, gain and
loss of function, linkage, haplotypes, positional cloning, geneXenviroment interactions
& epigenetics
• There will be at least one problem (~8 pts.) taken directly from either Assignment Set 8
or this review sheet
• The content of your final will be similar to the S11 & W10 finals (posted online)
• The Winter 2013 final was worth 90 pts:
Section 1: 58 pts includes material covered before (some) and after (mostly) the midterm
Section 2: 12 pts: choice of one of two options (reading comprehension & data analysis
– mostly material predating midterm)
Section 3: 20 pts: choice of two (10 pts each) of four options (new and old material)
 Option 1: Direct detection of genotype and other things
 Option 2: Genotype crunching and gene interactions
 Option 3: Probability Calculations
 Option 4: Choose one of two essay topics
• Be sure to memorize the size of the human genome and the estimated number of genes in
the human genome.
• Be sure to review these lectures as you may see a couple of content-oriented questions:
o From the last week of class: Complex traits, Epigenetics & DNA methylation
o From earlier in the quarter: Genome structure and DNA profiling
In addition to material covered most recently, be sure to review basic concepts:
• Chapter 1 of text
• Using models to explore biological processes
• Mendel, basic probability and basic pedigrees
• Polymorphic traits, alleles and sites
• Complications to Mendel including the complex relationship between genotype and
phenotype
• Complementation, suppressors, modifiers, epistatic interactions
• The molecular basis of mutation and the effect of mutation on gene function
• Look at reading comprehension and data analysis problems from Assignment Set 5 &
midterms exams
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Final Exam Study Problems ** means that ANSWERS will be available for this question.
 Problem -1 ** Wild-type foxgloves have single flowers. In a population of flowers
growing in British Columbia you discover a polymorphic variant that has double flowers. Pollen
from the double plant is used to fertilize a wild-type plant obtained from the same location in
BC. Two plants with double flowers are obtained from the cross. A second wild-type plant is
obtained from the same area. A cross from this plant with the same double plant yields 4 single
progeny. Assuming that this is a monogenic trait and that there are no complications, what
can you conclude about dominance? Your answer should include:
• Possible genotypes for each plant (be sure to define allele symbols)
• A statement about what you can or cannot conclude
• Be sure to support your conclusion with a clearly laid out set of arguments
• Don’t be fooled by sample sizes here and include some probability calculations if you
want
 Problem 0 Your mom sends you an email. She has read about a recent study indicating
that regions of the human genome are evolving and have been under intense selection in the past
5000-15000 years since “we” as a species abandoned the hunter-gatherer lifestyle and took up
agriculture. One gene that was discussed is this study is called the microcephaly (cephalon =
head) gene. The investigators presented evidence that selection for certain allelic variations in
this gene allowed our big brains to enlarge even further in the “recent” past. This gene had
previously been identified in a study of a loss-of-function mutation in a Pakistani family. Your
mom is puzzled by the name of this gene as it doesn’t seem to fit what she had read in the paper.
Based on your understanding of how genes have traditionally been named, briefly enlighten your
mother. Two sentences max.
 Problem 1 ** People with venous thrombosis suffer from blood that clots aggressively and
inappropriately. This phenotype results from a mutation in the gene that codes for Factor V.
This mutation (which we’ll call FVac for aggressive clotting) causes a single amino-acid
substitution. Wild-type Factor V protein acts to accelerate the body’s clotting process and is
normally under the control of a protein called APC that destroys Factor V after it has initiated the
clotting process. The mutant Factor V is impervious to APC’s attack. Homozygotes for this
mutant gene apparently show an even greater tendency to form clots than heterozygotes.
Based on the information given above choose True, False or not enough Information given.
T F I The FVac mutation is incompletely dominant to the wild-type allele.
T F I The FVac mutation is a gain-of-function mutation.
One sentence explanation
 Problem 2 More than 50% of severe childhood deafness is genetically determined.
Recessive, loss-of-function mutations in any one of at least thirty different genes (named DFNB1….. DFNB-30) can cause severe childhood deafness without any other abnormalities.
Recently 141 members of a large consanguineous (inbred) family segregating deafness
were examined using a DNA based test for a specific mutant allele of the DFNB-26 gene. The
frequency of this mutation allele in the general population is 0.0001. All deaf individuals (2
males and 6 females) were homozygous for the DFNB-26 mutation. Seven individuals with
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normal hearing were identified that were also homozygous for this mutant allele. Interestingly,
none of the deaf individuals, but all of the seven with normal hearing were found to
heterozygous for a second mutation in another DFNB gene. (Nature Genetics 26: 431 2000)
In 2-3 well-crafted sentences restate the content of this paragraph & use all the terms below
that are applicable [to this example]
pleiotropic sex-linked autosomal polymorphic
variably expressed
incomplete penetrance
genetic heterogeneity
dominant recessive
suppression/suppressor
modifier
complementation additive gene action epistasis/epistatic
Problem 3 ** A friend of yours gets a female cat from the pound that is deaf and has curled
ears. He mates this animal with a male who is normal for both of these traits and came from a
true-breeding normal line. Over a period of years, they produce a 4 of litters of kittens with the
following phenotypes.
Cross #1
deaf, curled female x wild-type male

#of kittens
Phenotype
10
deaf, curled ear
10
normal for both traits
Your friend concludes that both ear problems result from a single pleiotropic mutation.
Cross #2 Your friend selects a deaf, curled female cat who is one of the progeny from
Cross#1. He mates her to a normal brother. To his surprise, one of 14 kittens (a female) has
curled ears but is not deaf.
Explanation #1
• Assumes that both traits result from a single pleiotropic gene.
• Proposes that one of the parents of cross #1 was heterozygous for an unlinked recessive
suppressor mutation that is specific for the hearing defect.
Given this explanation, write out the genotypes of the parents of cross #2 and their curled
kitten: s+ = wild-type allele s= recessive suppressor allele
cd+ = wild-type cd = curled and deaf
Explanation #2 Provide a completely different* genetic explanation for his observations
from Cross #2. *This explanation cannot be variable expressivity due to developmental noise or
the environment.
• Define allele symbols and write out genotypes
• Propose a simple experiment to differentiate between the two explanations. You
experiment should include mating the curled cat.
Briefly describe experimental design and the predicted results. Outline your answer as follows:
• Experimental design:
• Predicted results is #1 is correct:
• Predicted results if #2 is correct:
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 Problem 4 About 5% of breast cancer cases are caused by an inherited susceptibility.
Familial, early-onset breast cancer can result from a loss-of-function mutation in either the
BRCA1 gene or the BRCA 2 gene.
a. The BRCA I gene codes for a protein (on chromosome 17) that is involved in repair of
double-strand breaks in DNA. Briefly explain why a defect in this function would increase the
probability of developing cancer in general. 2-3 sentences
• Your answer should include a very brief summary of the current model for the genetic basis
of cancer
• You do not need to address the issue of tissue-specificity
b. Explain the graph
With BRCA1 mutation: Notice that the probability of breast/ovarian cancer is not 100%. Also
there is variable expressivity among family members with respect to the age at which the cancer
appeared and which type cancer of developed. Recall our discussions in class of mechanisms
underlying incomplete penetrance and variable expressivity of genetic traits. We discussed three
general categories of factors that influence the phenotypic expression of a genetic trait. List
these three categories and briefly explain how each could affect the development of cancer
specifically. Give a specific relevant example of each.
Without BRCA I mutation: A women shown not to have the BRCA I mutations has the same
risk as the general population: 6% probability of developing breast cancer by age 70 and 1%
probability of ovarian cancer. Why do people with no inherited risk nonetheless develop these
cancers and why is it typically at an older age? two sentences
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 Problem 5 Gorlin syndrome is an autosomal dominant disorder that predisposes affected
individuals to various cancers and developmental defects, which are obvious at birth. Examine
the pedigrees on pg 2 of the DATA sheet. B1, B2 and B3 are alleles of a site (called D9S29)
that maps to chromosome 9. A genotype of B1 means that the individual was homozygous for
B1. (Likewise for B2 and B3). Each pedigree represents a different kindred group. Assume the
disease shows complete penetrance and that the D9S29 polymorphism is 4 map units from the
gene mutated in Gorlin syndrome.
a. In kinship 2601, there is a B2B3 individual in generation III and one in IV. One has the
disease the other does not. 1-2 sentences.
b. In kinship 2102, the
B1B2 male from
generation II contacts
you for some advice.
His wife is expecting
their third kid and a
prenatal test indicates a
genotype of B1B2.
First: Define allele
symbols for disease
genes and write out the
genotypes of the
parents using notation
for linked genes.
[Assume Gen III kids
are the products of
non-recombinant
gametes]
Second: Calculate the
probability that the kid
is heterozygous for the
Gorlin mutation.
Show your work and
circle your answer.
c. Examine kinship group 2342. Here are two possibilities for the genotype of the first
generation:
affected male B2B2 X unaffected female B1B2
OR
affected male B1B2 X unaffected female B2B2
Examine the entire pedigree. Which scenario is most likely? Circle your choice. No
explanation required.
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 Problem 6 ** Jack and Jill have a child with Down syndrome (trisomy 21). They
participate in a study to determine which parent contributed the abnormal gamete. In this study,
a chromosome 21 microsatellite (STR) site is examined using PCR and primers that flank the
microsatellite site. The data below shows the results of gel electrophoresis of PCR products
generated from genomic DNA isolated from the parents and three hypothetical results from the
child. Heavier bands indicate bands with double-intensity of staining. Note that this analysis is
equivalent to a DNA fingerprinting gel and does not involve any restriction digest of the PCR
products.
Non-disjunction refers to a situation where either: (i) pair of homologs fail to separate in
anaphase of meiosis I and end up in the same daughter cell OR sister chromatids fail to separate
in anaphase II. For each hypothetical result (HR) indicate which parent contributed the
abnormal gamete and in which meiotic division the non-disjunction event occurred. Assume that
no recombination has occurred between the centromere and the microsatellite site during the
generation of the gametes. If the results are inconclusive, indicate so and briefly explain.
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 Problem 7 ** Prader-Willi syndrome (PWS) is characterized by short stature, obesity
and mental retardation. It is normally caused by a deletion (of a chunk of the chromosome)
on the paternally derived copy of chromosome 15. Deletions of the same region of the
maternal chromosome do not cause PWS. The corresponding region in the maternally
derived chromosome is inactivated during oogenesis by a process known as genomic
imprinting which involves silencing of the maternal allele via CpG methylation (see
epigenetics lecture). This process is normal for this region of chromosome 15. [But
imprinting occurs only rarely in the genome.]
In the family shown below, neither parent has PWS. The trait shows complete
penetrance. [In contrast to the usual type of PWS mutation, the father in this family does not
have a deletion on either copy of chromosome 15 (data not shown)]. The agarose gel shows
an STR polymorphism that has been tracked using PCR and is linked to the region of
chromosome 15 associated with PWS. STR polymorphisms on other autosomes confirm that
individual #3 is the father of #2.
Larger PCR products
Ô
Smaller PCR products
The lane numbers on the agarose
gel correspond to numbers on the
pedigree. Note that this analysis
is equivalent to a DNA
fingerprinting gel and does not
involve any restriction digest of
the PCR products.
1
2
3
4
5
(i). Examine the gel. What does the difference in band size represent? In other words, what is
the molecular basis of the polymorphism. One sentence.
(ii). Examine the data shown above. What is surprising about the genotype of the affected child
(#2)? Be explicit. NOTE: ignore the faint bands in the gel; only anayze the dark bands.
(iii). Read about non-disjunction in your text. The gamete that #2 received from his mother was
produced by non-disjunction of chromosome 15 during meiosis in her germline. Assuming no
crossing-over between the site of the microsatellite polymorphism and the centromere, in which
meiotic division did the non-disjunction event occur? Circle the correct answer:
a. Meiosis I
a. Meiosis II
c. either Meiosis I or II
d. cannot determine from the information given
Explain your answer with a diagram and one or two sentences of text:
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Problem 7 continues on the next pagr
(iv) Now assume that a cross-over event did occur between the site of the microsatellite
polymorphism and the centromere. In which meiotic division did the non-disjunction event
occur? Circle the correct answer:
a. Meiosis I
a. Meiosis II
c. either Meiosis I or II
d. cannot determine from the information given
 Problem 8
Risk or likelihood of a particular phenotype. By definition the wild-type genotype with no
environmental exposure has a risk of 1.0.
Part A: In 1-2 sentences summarize the main point(s) from Panel A.
Part B: In 1-2 sentences summarize the main point(s) from Panel B
Part C: State explicitly the main difference(s) between panels A and B. 1-2 sentences max.
Part D: Recall the discussion of phenylketonuria in your text. Does either panel accurately
reflect the gene X environment interaction seen in this disease state? {NOTE: no need to
memorize details of PKU or any other trait or disease state. Questions of this sort would give
you G X E info and you would be asked if it fit these models.}
Part E: Review depression polymorph data from lecture on complex traits. Does either
panel accurately reflect the gene X environment interaction seen in the data sets? {NOTE: no
need to memorize details of paper. Question of this sort would give you G X E info and you
would be asked if it fit these models.}
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 Problem 9 *Hints but not a complete answer will be available
Panel A
Panel B
Shaded circles = Affected (Addictive personality)
Unshaded and double circles = Unaffected
Risk = contributes to addictive personality
Each risk allele is presented as a puzzle piece of a different color or shape. Assume that
different shapes indicate alleles of different genes and that the same shape but different color
indicates alleles of the same gene
This figure is taken from a review article on the genetics of addictive behaviors. You are charged
with writing an article for the New York Times that includes this figure. Examine it carefully and
write an essay explaining/interpreting panels A and B. Be sure to address all aspects of each
panel.
• Your answer should be several sentences long and should throughly explain each type of
symbol and the difference in patterns in A and B.
• Be sure to address the underlying causes of the double-circled symbols
• You must use proper terminology. See extra sheet for a list of terms that we have examined.
Be sure to apply all appropriate terms.
• Take some time to organize your thoughts and start with a list of points that you want to
make. NOTE: your answer should be in essay form -- the list is for you.
• Put your answer on an extra sheet of paper or on the back of this exam.
A list of terms that may be useful
• suppression
variable expressivity
recessive lethal
• incomplete penetrance
polymorphic
sex-limited/sex-influenced
• pleiotropic
genetic heterogeneity (heterogeneous trait)
• complementation epistasis
modifier
haploinsufficient
• multifactorial polygenic genetic background stochastic effects
• probabilistic propensity monogenic
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ESSAY QUESTION
“We used to think our fate was in the stars. Now we know, in large measure our fate is in our
genes.” James Watson, 1989.
“Genetic determinism is one of those simpleminded errors that we are prone to commit when we
think that genes are linked to diseases in a kind of inevitable fashion.... It invites you to think that
‘genes equal fate.’ ” Thomas Murray (ethicist)
Many scientists are concerned that the flood of information available about human genetics and
the human genome will lead to misunderstandings about the complexity of the relationship
between genetic variation and the expression of a specific trait or disease. Based on what you
have learned in this class about the relationship between genotype and phenotypes, fully analyze
this issue of genetic determinism. NOTE: This should not be an essay concerning ethics or
morality. This essay should deal with the science of biology and genetics only. Provide
arguments/examples that support both quotes.
ESSAY QUESTION
Defining Disease in the Genomic Era: “……..Human genomic sequencing will reveal
thousands of genetic variations among individuals that many will assume are associated with
disease. But translating such genotypic differences into phenotypic states is prone to pitfalls…”
Your mother has read this statement and doesn’t understand exactly what it means. Write
an essay explaining this quote to your mom. Be sure to illustrate your essay with specific
examples: real or hypothetical (either is OK). Cast a broad net in your answer to this question
and be systematic with your analysis. In other words, you might start with an random SNP
(located somewhere in the human genome) and go from there…
There are a number of different points that need to be considered here. Some overlap
with the first essay question. Others don’t.
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