Exam I Practice PHS 112 Pharmacogenomics
1. Describe the differences between nonsense and missense mutations.
2. You are investigating the hypothesis that a gene that is Y-linked (such as the one for the
human porcupine trait). If your hypothesis were correct you would expect an affected man to
answer each of the following questions with a “yes” except: (You can assume that the condition
is very rare)
A. Do all your father’s brothers have the condition?
B. Do all of your brothers have the condition?
C. Do all your sons have the condition?
D. Do your mother’s brothers have the condition?
E. All would be correct.
3. Certain recessive genes cause profound hereditary deafness, and individuals homozygous for
such genes are occasionally found in high frequencies among extended families in small, isolated
communities. The mutations originate in individuals several generations in the past, and become
homozygous through marriages among relatives. A deaf man and a deaf woman from two
different communities, each having deaf parents, had three children all of whom had normal
hearing. How would you explain this?
4. Define locus heterogeneity and describe how it might cause confusion in genetic mapping
studies.
5. A color-blind woman married a man with normal vision. She had a daughter who, she was
glad to find, had normal vision. Her daughter married a man with normal vision. What should
she tell her daughter about the probability of having color-blind children?
6. Define dominance (of a genetic trait). Please provide an explanation of how dominance might
occur.
7. Describe the difference between an allele and a locus?
8. Define pleiotropy. Can you give an example?
9. Please explain what is meant by the statement “The genetic background a mutation finds itself
in will have an impact on phenotype”.
10. Why would redefining a clinical phenotype to the most extreme case help in a genetic
mapping study?
11. Please describe the difference between cis- and trans-acting factors in gene regulation. Give
an example of each
12. Eukaryotic mRNAs are generally all of the following except:
A. transcribed by RNA Polymerase II
B. 7mG capped, spliced to remove introns, and tailed with poly(A)
C. the most abundant type RNA in a cell
D. lacking promoter and enhancer sequences but containing 5’and 3’ untranslated regions
E. colinear with the proteins they encode
13. It has be said that gene regulation via signal transduction (for example, the cyclic AMP
pathway) is highly adaptable in that the system can be used by a variety of signaling molecules
simply by changing the receptor. Please explain.
14. Which of the following genotypes is homozygous?
A) AaBB
B) aABB
C) aaBB
D) aaBb
E) AaBb
15. Complete the pedigree (second and third generations) below if the trait being analyzed is Ylinked recessive. Assume that individual A is phenotypically normal:
16. Define Epistasis. Can you give an example?
17. Please describe how epigenetic mechanisms of gene regulation are different from other
mechanisms of gene regulation and give an example.
18. What are silent site substitutions? What is the molecular explanation for how they arise?
19. Several mutations on the human X chromosome impart color blindness. A color-blind man and
his wife, with normal vision, have a color-blind daughter. What is the probability that their son
will also be color-blind?
Their color-blind daughter meets and marries (or not) a man with normal vision. What should
you tell these parents about the probability of having color-blind children? Please be specific.
20. You are planning to conduct a large genetic mapping study to identify gene(s) involved with
poor response to a new drug. Please describe; 1) Genetic background; and 2) Two methods you
might use to help control for this problem in your study.
21. What is a transcription factor?
22. Huntington's Disease (HD) is a devastating, degenerative brain disorder for which there is, at
present, no effective treatment or cure. Symptoms usually appear in adults within the third or
fourth decade of life and result in death within 10 to 20 years. HD is an autosomal dominant
disease. A young patient, whose paternal grandfather died of HD (grandmother lived to be
102!!!) and whose parents (age 27) are as yet healthy would like to know whether she should be
worried. Her maternal grandparents are both healthy and free of HD. What would you advise her
concerning the probability of her having HD?
One out of every 10,000 Americans has HD. Can you explain why selection has not removed this
lethal autosomal dominant allele?
23. Please describe the Infinite Allele Model. Why are the assumptions of this model important
in conducting genetic mapping studies?
24. Please describe the “rare allele” effect and why it is important.
25. Choose any three of the five scientists listed below and describe their contribution to
genetics/genomics.
Charles Darwin, Gregor Mendel, Thomas Hunt Morgan, Archibald Garrod, Rosiland Franklin
26. What is a promoter? Would mapping studies be able to detect polymorphisms in promoters?
Please explain.
27. Consider the trait used in class. “Tongue rolling” is determined by a single gene with two
alleles;
“T” allele → the ability to roll tongue, dominant, allele frequency = 0.447
“t” allele → cannot roll tongue, recessive, allele frequency = 0.553
If this gene were not autosomal, but was instead located on the X chromosome please answer the
questions below.
a) Frequency of males who can roll their tongues?
b) Frequency of females who cannot roll their tongues?
c) If there were 100 individuals (50 males and 50 females) in our class how many would
be able to roll their tongues? Please show your work.
28. Please describe the difference between pleiotropy and epistasis.
29. The mutation the causes Tay-Sachs disease, a autosomal recessive neurodegenerative disease
that leads to death usually before the age of 5 years has remained in human populations for many
hundreds of generations. Please explain why this mutation persists in human populations despite
its huge selective disadvantage.
30. You are planning to conduct a large genetic mapping study to identify gene(s) involved with
poor response to a new drug. Please describe; 1) Environmental effects; and 2) Two methods you
might use to help control for this problem in your study.
31. What are transcription factors? Why are transcription factors often popular drug targets? Can
you describe one of the concerns in using transcription factors as drug targets?
32. Briefly describe the concept of ligand-inducible transcription factors in gene regulation. Can
you provide an example?
33. Please describe “phenocopies”, AND the role of phenocopies in genetic mapping studies.
34. What are silent site substitutions? What is the molecular explanation for these mutations?
36) Please describe the basics of “ligand-inducible transcription factors” as a mechanism of gene
regulation.
37) Some traits are said to be “complex genetic traits” in that the phenotype does not seem to
follow simple Mendelian patterns of inheritance. Please describe three reasons why some traits
exhibit complex patterns of inheritance.
38) It has been said that gene regulation via signal transduction (for example, g-protein coupled
cyclic AMP pathways) can result in magnification of the initial signal. Please explain.
39) What are phenocopies AND what strategies might one use to control for their effects in a
genetic mapping study.
40) Most single locus genetic mutations are recessive. Please describe what is meant by this
statement AND provide an explanation of why mutations are generally recessive.
41) In most cases mutations in genes that code for transcription factors are more debilitating than
mutations in genes that code for enzymes, transporters or receptors. Can you explain why this
might be so?
42) It is well established that many, if not most, human traits are polygenic or multifactorial.
Some traits like height or intelligence show continuous variation among individuals while others,
like cleft palate and some cancers, are not continuous in their expression, but are discrete
(present or not present). Please explain how a polygenic trait could exhibit this “all or none”
expression.
43) It has been found that haplotypes or haplotype blocks vary in size among human populations.
Please describe what a haplotype block is AND why populations (native Americans vs native
South Africans) might vary in the size of their haplotype blocks.
The Y chromosome comprises a single haplotype block, can you provide a explanation why this
might be so?
44) Often a given mutation or variant will have slightly different phenotypes in different groups
of patients. “Genetic Background” is frequently used to explain how the same exact mutation
could exhibit different phenotypes in different populations. Please explain.