1.
A sample of human DNA is
subjected to increasing temperature until the major fraction exhibits optical
density changes due to disruption of its helix (melting or denaturation). A
smaller fraction is atypical in that it requires a much higher temperature for
melting. This smaller, atypical fraction of DNA must contain a higher content
of
A. 
B. 
C. 
D. 
E. 
2.
A newborn baby has a sibling
with sickle cell anemia (141900) and is at risk for the disease. Which of the
following is the appropriate diagnostic test for sickle cell anemia in this
baby?
A. 
B. 
C. 
D. 
E. 
3.
. A farming couple in Northern Michigan consult their physician about severe
skin rashes and ulcers noted over the past year. They also have lost many
cattle over the past year, and claim that their cattle feed changed in
consistency and smell about 1 year ago. Chemical analysis of the feed shows
high concentrations of polychlorinated biphenyls, a fertilizer related to known
carcinogens. The physician sends the chemical to a laboratory for carcinogen
testing, which is performed initially and rapidly by
A. 
Inoculation of the chemical into nude mice
B. 
Incubation of mutant bacteria with the chemical to measure the rate of reverse or "back" mutations
C. 
Incubation with stimulated white blood cells to measure the impact on DNA replication
D. 
Computer modeling based on the structures of related carcinogens
E. 
Incubation with mammalian cell cultures to measure the rates of malignant transformation
4.
Patients with hereditary
nonpolyposis colon cancer [HNPCC (114500)] have genes with microsatellite
instability, that is, many regions containing abnormal, small loops of unpaired
DNA. This is a result of a mutation affecting
A. 
B. 
C. 
D. 
E. 
Nucleotide excision repair
5.
A culture of bacteria not
resistant to tetracycline develops an infection from a virus that is derived
from the lysis of tetracycline-resistant bacteria. Most of the bacterial
progeny of the original culture is found to have become resistant to
tetracycline. What phenomenon has occurred?
A. 
B. 
C. 
D. 
E. 
6.
Which of the following molecules is found in a
nucleoside?
A. 
B. 
A 1' base linked to a pentose sugar
C. 
A 5'-phosphate group linked to a pentose sugar
D. 
A 3'-phosphate group linked to a pentose sugar
E. 
7.
Which of the following enzymes
can be described as a DNA-dependent RNA polymerase?
A. 
B. 
C. 
D. 
E. 
8.
. The DNA sequence M, shown
below, is the sense strand from a coding region known to be a mutational
"hot spot" for a gene. It encodes amino acids 21 to 25. Given the
genetic and amino acid codes CCC = proline (P), GCC = alanine (A), TTC =
phenylalanine (F), and TAG = stop codon, which of the following sequences is a
frame-shift mutation that causes termination of the encoded protein?
M 5'-CCC-CCT-AGG-TTC-AGG-3'
A. 
B. 
C. 
D. 
E. 
9.
The hypothetical
"stimulin" gene contains two exons that encode a protein of 100 amino
acids. They are separated by an intron of 100 bp beginning after the codon for
amino acid 10. Stimulin messenger RNA (mRNA) has 5' and 3' untranslated regions
of 70 and 30 nucleotides, respectively. A complementary DNA (cDNA) made from
mature stimulin RNA would have which of the following sizes?
A. 
B. 
C. 
D. 
E. 
10.
The hypothetical
"stimulin" gene with two exons encoding a protein of 100 amino acids
is found to have abnormal expression in cell culture. Which of the following
mutations would produce a 500-bp stimulin mRNA and a 133–amino acid peptide
that reacts with antibodies to stimulin protein?
A. 
Splice junction mutation preventing RNA splicing
B. 
Frame-shift mutation in codon #2
C. 
Silent point mutation in the third nucleotide of codon #50
D. 
Nonsense mutation at codon #2
E. 
11.
Template-directed RNA
synthesis occurs in which of the following?
A. 
B. 
C. 
Initiation of the polymerase chain reaction
D. 
E. 
Repair of thymine dimmers
12.
Which of the following most correctly describes
mammalian messenger RNAs?
A. 
They are usually transcribed from both DNA strands
B. 
They are normally double-stranded
C. 
Their content of uridine equals their content of adenine
D. 
They have an overall negative charge at neutral pH
E. 
Their ratio of ribose to purine bases equals 1
13.
The western blot uses what
type of probe?
A. 
B. 
C. 
Products of polymerase chain reaction (PCR)
D. 
E. 
Mutant and normal oligonucleotides
14.
How many high-energy
phosphate-bond equivalents are utilized in the process of activation of amino
acids for protein synthesis?
A. 
B. 
C. 
D. 
E. 
15.
An immigrant family from
rural Mexico
brings their 3-month-old child to the emergency room because of whistling
inspiration (stridor) and high fever. The child's physician is perplexed
because the throat examination shows a gray membrane almost occluding the
larynx. A senior physician recognizes diphtheria, now rare in immunized populations.
The child is intubated, antitoxin is administered, and antibiotic therapy is
initiated. Diphtheria toxin is often lethal in unimmunized persons because it
A. 
Inhibits initiation of protein synthesis by preventing the binding of GTP to the 40S ribosomal subunit
B. 
Binds to the signal recognition particle receptor on the cytoplasmic face of the endoplasmic reticulum receptor
C. 
Shuts off signal peptidase
D. 
Blocks elongation of proteins by inactivating elongation factor 2 (EF-2, or translocase)
E. 
Causes deletions of amino acid by speeding up the movement of peptidyl-tRNA from the A site to the P site
16.
Methionyl–transfer (t) RNA is used for
initiation of protein synthesis by which of the following?
A. 
B. 
Eukaryotic mitochondrial ribosomes
C. 
Eukaryotic cytoplasmic ribosomes
D. 
E. 
17.
Which of the following is
required for certain types of eukaryotic protein synthesis but not for
prokaryotic protein synthesis?
A. 
B. 
C. 
Signal recognition particle
D. 
E. 
18.
A major obstacle to gene
therapy involves the difficulty of homologous gene replacement. Which of the
following strategies addresses this issue?
A. 
A recombinant vector contains complementary DNA sequences that will facilitate site-specific recombination
B. 
A recombinant vector expresses antisense nucleotides that will hybridize with the targeted mRNA
C. 
A recombinant vector replaces inessential viral genes with a functional human gene
D. 
A recombinant vector transfects patient cells, which are returned to the patient
E. 
A recombinant vector contains DNA sequences that target its expressed protein to lysosomes
19.
A family in which several
individuals have arthritis and detached retina is diagnosed with Stickler
syndrome. The locus for Stickler syndrome has been mapped near that for type II
collagen on chromosome 12, and mutations in the COL2A1 gene have been described
in Stickler syndrome. The family became interested in molecular diagnosis to
distinguish normal from mildly affected individuals. Which of the following
results would be expected in an individual with a promoter mutation at one
COL2A1 gene locus?
A. 
Western blotting detects no type II collagen chains
B. 
Southern blotting using intronic restriction sites yields normal restriction fragment sizes
C. 
Reverse transcriptase–polymerase chain reaction (RT-PCR) detects one-half normal amounts of COL2A1 mRNA in affected individuals
D. 
Fluorescent in situ hybridization (FISH) analysis using a COL2A1 probe detects signals on only one chromosome 12
E. 
DNA sequencing reveals a single nucleotide difference between homologous COL2A1 exons
20.
Gyrate atrophy (258870) is a
rare autosomal recessive genetic disorder caused by a deficiency of ornithine
aminotransferase. Affected individuals experience progressive chorioretinal
degeneration. The gene for ornithine aminotransferase has been cloned, its
structure has been determined, and mutations in affected individuals have been
extensively studied. Which of the mutations listed below best fits with test
results showing normal Southern blots with probes from all ornithine
aminotransferase exons but absent enzymatic activity?
A. 
Duplication of entire gene
B. 
Two-kb deletion in coding region of gene
C. 
Two-kb insertion in coding region of gene
D. 
E. 
21.
. Hurler's syndrome (252800)
is caused by a deficiency of L-iduronidase, an enzyme normally expressed in
most human cell types. It was demonstrated by Neufeld that exogenous
L-iduronidase could be taken up by deficient cells via a targeting signal that
directed the enzyme to its normal lysosomal location. Which of the following
therapeutic strategies would be the most realistic and efficient mode of
therapy?
A. 
B. 
Heterologous bone marrow transplant
C. 
Infection with a disabled adenovirus vector that carries the L-iduronidase gene
D. 
Injection with L-iduronidase purified from human liver
E. 
Autologous bone marrow transplant after transfection with a virus carrying the L-iduronidase gene
22.
Which of the following
mutations is most likely to be lethal?
A. 
Substitution of adenine for cytosine
B. 
Substitution of cytosine for guanine
C. 
Substitution of methylcytosine for cytosine
D. 
Deletion of three nucleotides
E. 
Insertion of one nucleotide
23.
. In the following partial
sequence of mRNA, a mutation of the template DNA results in a change in codon
91 to UAA. What type of mutation is it?
88
89
90
91
92
93
94
GUC
GAC
CAG
UAG
GGC
UAA
CCG
A. 
B. 
C. 
D. 
E. 
24.
Which one of the following
causes a frame-shift mutation?
A. 
B. 
C. 
D. 
Substitution of purine for pyrimidine
E. 
Substitution of pyrimidine for purine
25.
Which of the following regulators are said to
act in "cis"?
A. 
The lac repressor and mammalian transcription factors
B. 
The lac repressor and the lac operator
C. 
The lac operator and mammalian enhancers
D. 
The lac operator and mammalian transcription factors
E. 
Mammalian transcription factors and enhancers