Human Genetics
May 2000
Exam 1
There are 20 questions. Each is worth 5 points. One bailout question is given at the end.
1. (In this question, I am interested in both patterns of inheritance and correct pedigree
notation.) The gene for “hairy ears” is on the Y chromosome. On the pedigree below,
use appropriate pedigree notation to identify every generation and each individual within
each generation. The father in the first generation expresses the “hairy ear” gene,
Highlight him and every individual in this pedigree who will also express this gene. Also,
if applicable, identify any female carriers.
2. A) In a study published in 1956, Paul Polani found that out of 25 Turner syndrome
females, four were color blind. The normal incidence for color blindness in females is
<0.01%. How would you explain Dr. Polani’s finding?
B) In a similar study, you find that, while normal male have an incidence of color
blindness of up to 15%, Kleinfelter males have an incidence of color blindness of <0.1%.
How would you explain your finding?
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3. a) What is the most common risk factor for Down’s syndrome? ______________
b) What is the specific chromosome abnormality associated with most cases of this
syndrome?___________
c) There are very rare cases in which one member of a pair of identical twins has Down’s
syndrome while the other member has both a normal karyotype and a normal phenotype.
Propose a mechanism for how this might happen.
4. You are interested in the gene that codes for a common recessive genetic disorder. It
is associated with a gene that codes for a protein that is only expressed in T
lymphocyte cells. Briefly outline a strategy for how you might generate an EST for this
gene.
5. Once you have generated an EST for this gene, briefly identify and describe a technique
you might use to apply this probe in finding the location of this gene on a particular
chromosome.
6. The Alu family of short interspersed repeated DNA elements are distributed
throughout primate genomes. Alu sequences are thought to be derived from the 7SL
RNA gene, which encodes the RNA component of the signal recognition particle that
functions in protein synthesis. Now there are over 700,000 non-functional copies of
ALU interspersed throughout the human genome. Briefly explain how that came to be.
What is the molecular mechanism of how ALU became inserted throughout the genome?
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7. What is the name of the plot that is shown
at the right?
Give an example of a specific type of DNA
that would be found in the “fast” region.
How would you prepare the DNA for this type
of analysis?
8. Briefly diagram and explain in words how the approach of the Human Genome Project is
different from the gene mapping approach of the private Celera Labs.
9. In a study published in 1998, it was found that a single nucleotide polymorphism in the
serotonin receptor gene leads to either a long or short version of the protein product of
this gene. If you wanted to develop a rapid assay to test whether people carried this
polymorphism, what technique would you use? Very briefly describe the components you
would need to run this test.
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10. These illustrations were taken from the Human Genetics Tutorial at “the Biology Place”
at the University of Arizona. The arrows in the picture at the left show the restriction
sites for normal beta globin and sickle cell beta globin DNA. These DNA samples were cut
by a this restriction enzyme, and run on an electrophoresis gel.
a) Label the lanes in the figure on the right as either normal, or sickle cell DNA.
b) To see the cut DNA, they used a small DNA molecule labeled with a fluorescent
molecule. (the probe) On the picture at the left clearly circle the regions to which the
“probe” would bind.
11. This question refers to the same diagrams as the previous
question. In the box below, draw the pattern that you would see for an individual who is a
carrier of the sickle cell trait.
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12. This is a hypothetical situation, because, I am sure that if it really happened, it would
be lethal. Imagine that the parents of a newborne XX female patient consult you about
their baby who has a diffeciency in the XIST gene. She cannot make any of the XIST
gene product.
a) What quick simple technique could you use to diagnose this condidition?
b) Even though this is just a single gene defect, I think it would have profound lethal
consequences and she would die within the first year of life. What is the reason that this
defect would be so profoundly lethal?
13. Briefly describe how you might use (GT)n repeated sequences as markers for
identification of a particular individual. What techniques would you use? What might
you use to detect the sequences?
14. In constructing a hybrid somatic cell line, how are the cells fused?
What is a hybrid somatic cell line used for?
15. Male pattern baldness is a sex influenced gene. It is always expressed when an
individual inherits two copies of the gene but, for indivduals who inherit only one copy of
the gene, it is only expressed in the presence of dihydroxy testosterone. Both Christy
and her sister Rose are loosing their hair. Their 45 year old brother, Daryl has a full
head of hair. Their father is bald but their mother is phenotypically normal. What are
the possible genotypes of each of these individuals?
Father
Mother
Christy and Rose
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Daryl
16. Suppose you found out that Daryl was phenotypically a female until the age of 14. How
might that change the possible male pattern baldness genotypes for all the family
members?
Father
Mother
Daryl
Christy and Rose
Explain your answer:
17. Many years ago, Fergeson-Smith hypothesized that the genes repsonsible for Turner
syndrome would be the X-linked genes that escape inactivation and have homologous
genes on the Y chromosome. David Page has found a candidate gene (RPS4) that seems
to fit these criteria.
a) In which region of the X and Y chromosomes is this gene located?
b) How does this gene escape X inactivation?
18. You are a genetic counelor who has been asked to consult on a newborne baby who has a
profound defect in salt metabolism. You ask for a karyotype and a test for a specific
sex hormone.
What will the karyotype show you?
What disease do you suspect?
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19. This question comes from Chapter 9 of your book. Duchene Muscular Dystrophy is an
X-linked recessive disease. The gene associated with this disease was identified using
deletion mapping. A boy with DMD and 3 other X linked diseases was found to have a
deletion on Xp21.2. Researchers used this boy’s DNA and DNA from a normal X
chromosome to clone a fragment of normal DNA from this region. Very briefly outline the
key steps in how this was done.
20. What is the difference between RFLPs and VNTRs? They are both different types of
polymorphisms causing different individuals to have unique banding patterns, but what
exactly distinguishes one polymorphism from another? And what kinds of probe might
you use to detect the bands?
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Bail Out A certain X-linked dominant disease in humans occurs when there are more than
40 repeats of a CGG trinucleotide in a particular gene. The unique sequence outside the
repeat
region is as follows:
5' CAGTATGCA------(CGG)n-------ATGCGTAAT 3'
3' GTCATACGT------(GCC)n-------TACGCATTA 5'
Shown on the right are the
outline of a pedigree for the disease
described above, and a
representation of a gel showing
fragments detecting the number of
CGG repeats. The DNA
corresponding to each individual is
directly below his or her place in the
pedigree. Based on the information
you have been given, fill in the
pedigree to show the sex of the
individual as well as the phenotype (affected vs. unaffected).
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