Chapter 11—The Direct Detection of Genotype Distinguishes Individual Genomes
Fill in the Blank
1. From a single cell removed from the embryo of Cfcf parents to produce a high copy
number DNA fragment with the CF mutation, the _________ technique was used.
Ans: PCR
Difficulty: 2
2. For the ____________ technique, two short single strand DNA sequences called
____________ complementary to the CF gene are needed.
Ans: PCR, primers
Difficulty: 1
3. When it is possible to follow the segregation of one or more alternative alleles at a
particular locus with DNA probes or PCR-based analyses, researchers consider the locus
______________.
Ans: polymorphic
Difficulty: 2
4. The approximate number of microsatellites in the human genome is
_________________.
Ans: 100,000
Difficulty: 2
5. In minisatellites the number of bases (in the “boxcar”) is ____________.
Ans: 10-40
Difficulty: 3
6. A contraction of phrases from “haploid genotype” _____________.
Ans: haplotype
Difficulty: 1
7. The units used for a genetic map are __________; the units used for a physical map are
____________.
Ans: centimorgan(cM); kilobasepairs (kbp)
Difficulty: 2
8. Mutant alleles that show only a predisposition toward a mutant or disease phenotype
show ________________.
Ans: incomplete penetrance
Difficulty: 2
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9. Traits that arise in the absence of a mutant genotype because of an environmental
treatment are known as ____________________.
Ans: phenocopies
Difficulty: 2
10. Different combinations of alleles at multiple loci that result in measurable differences in
phenotype are known as ______________________ loci.
Ans: quantitative trait
Difficulty: 2
11. An _____________ is one of two or more alternative DNA sequences found at a locus,
either coding or noncoding, in different homologs of the same chromosome.
Ans: allele
Difficulty: 1
12. _________________ protocols can produce a quick snapshot of a combination of
genomic features that can identify an individual.
Ans: genotype
Difficulty: 1
13. Short oligonucleotides of 18-24 bases that can hybridize to only one of the two alleles at
a SNP locus under appropriate conditions are known as
_______________________________________.
Ans: ASO – allele specific oligonucleotides
Difficulty: 2
14. A piece of foreign DNA that has been inserted into an organism's genome through
experimental manipulation of early-stage embryos or germ cells is called a
_________________________.
Ans: transgene
Difficulty: 2
Multiple Choice
15.
A)
B)
C)
D)
E)
If the parents are Cfcf, the chance that any future child will be Cfcf is:
1/1.
1/3.
1/4.
1/2.
0.
Ans: D
Difficulty: 1
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16. If a PCR amplified sample hybridizes with two allele specific probes, one normal and
one mutant sequence, a carrier is identified if:
A) both samples give a signal.
B) neither sample gives a signal.
C) only the mutant probe gives a signal.
D) only the non-mutant probe gives a signal.
E) none of the above
Ans: A
Difficulty: 2
17.
A)
B)
C)
D)
E)
Molecular geneticists equate an allele with:
only transcribed genes.
only non-transcribed DNA.
any DNA site that is different among genomes.
any DNA site that is different among coding genomes.
any DNA site that is different among non-coding genomes.
Ans: C
Difficulty: 3
18. When the 250 kb region that encompass the Cf gene is sequenced in two CfCf
individuals, it is found that on the average the following number of base sequences is
different between them.
A) 0
B) less than 100
C) 350
D) 700
E) 1,000
Ans: D
Difficulty: 4
19. For a gene or a locus to be considered polymorphic it must satisfy the following two
conditions:
A) must be present in all males and females.
B) must be present in two or more sequence variations in at least 10% of the population.
C) must be present in two or more sequence variations in at least 1% of the population.
D) must be present in two or more sequence variations in at least 10% of children since not
all may reach adulthood.
E) must be present in two or more sequence variations in at least 1% of children since not
all may reach adulthood.
Ans: C
Difficulty: 4
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20. When two haploid genomes are compared, about how many base sequence differences
can be found in the non-coding DNA?
A) 3.4 billion
B) 3.4 million
C) 340 thousand
D) 34 thousand
E) 3.4 thousand
Ans: B
Difficulty: 3
21.
A)
B)
C)
D)
E)
Which is the most frequent cause of DNA polymorphism?
single base differences
duplications
inversions
translocations
ploidy
Ans: A
Difficulty: 1
22.
A)
B)
C)
D)
E)
In microsatellites, one, two or three base sequences are tandemly repeated about:
one million times.
one hundred thousand times.
one thousand times.
two hundred times.
15-100 times.
Ans: E
Difficulty: 2
23.
A)
B)
C)
D)
E)
The human genome contains approximately how many microsatellites?
one million
one hundred thousand
ten thousand
one thousand
one hundred
Ans: B
Difficulty: 3
24.
A)
B)
C)
D)
E)
Which of the following is the main source of variation in microsatellites?
chemicals in water
chemicals in food
ultraviolet light
background radiation
faulty DNA replication
Ans: E
Difficulty: 3
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25.
A)
B)
C)
Microsatellites compared to coding genes show:
more variation.
less variation.
about the same variation.
Ans: A
Difficulty: 2
26.
A)
B)
C)
D)
E)
Deletions, duplications and insertions have the following number of bases.
1
10
100
1000
from one to megabase
Ans: E
Difficulty: 3
27.
A)
B)
C)
D)
E)
Deletions, and duplications are most often caused by:
ultraviolet light.
ionizing radiation.
unequal crossing over.
all of the above.
b and c only
Ans: E
Difficulty: 3
28.
A)
B)
C)
D)
E)
Restriction sites provide substrates for:
DNA endonucleases.
enzymes that cut double stranded DNA.
enzymes which cut the ends of DNA.
a and b only
b and c only
Ans: D
Difficulty: 3
29.
A)
B)
C)
Three sequential restriction sites will produce how many fragments?
3
2
1
Ans: B
Difficulty: 1
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30. If the middle of three sequential restriction sites undergoes mutation, how many
fragments will be expected?
A) 3
B) 2
C) 1
Ans: C
Difficulty: 1
31.
A)
B)
C)
D)
E)
Allele-specific probes are:
dependent on PCR.
should be 20 or less bases long.
should be around 50 bases long.
a and b
a and c
Ans: D
Difficulty: 4
32. Lack of strong hybridization by an allele specific probe of about 20 bases to DNA to be
tested detects:
A) a normal, unchanged sequence.
B) a polymorphic sequence.
C) the probe is too short.
D) the probe is too long.
E) inappropriate protocol.
Ans: D
Difficulty: 4
33.
A)
B)
C)
D)
E)
The strength of holding of a probe and the DNA to be tested together depends on:
length of the probe.
temperature chosen during hybridization.
ionic strength of post-hybridization washes.
a and b
a, b and c
Ans: E
Difficulty: 3
34.
A)
B)
C)
D)
E)
With the microsatellite analysis feature, all of the following apply except:
must know the sequence of flanking markers.
must know the sequence of the repeat units in the microsatellite.
polymorhism is a matter of DNA size.
electrophoresis.
PCR.
Ans: B
Difficulty: 2
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35.
A)
B)
C)
D)
E)
Huntington disease is caused by:
a closely linked marker allele.
less than 34 CAG repeats.
base-pair substitution.
recessive allele.
42 or more CAG repeats.
Ans: E
Difficulty: 4
36.
A)
B)
C)
D)
Positional cloning requires:
knowledge about the function of a gene.
knowledge about the expression pattern of a gene.
knowledge about the map location of a gene.
knowledge about the sequence of a gene.
Ans: C
Difficulty: 3
37. Below are several steps involved in positional cloning. From the choices available, pick
the order of steps that would be successful.
1. Examining Northerns for candidate genes in specific tissues.
2. Obtaining DNA or cells from members of a family with an inherited disease.
3. Obtain a molecular marker that fails to recombine with the disease gene.
4. Examine sequences of possible exons.
5. Perform linkage analysis with known markers to determine linkage to a
chromosome arm.
A) Order 1, 2, 3, 4, 5
B) Order 3, 2, 1, 4, 5
C) Order 5, 3, 4, 1, 2
D) Order 2, 5, 3, 1, 4
Ans: B
Difficulty: 3
38.
A)
B)
C)
D)
Phenocopies of genetic diseases can arise:
from environmental stimuli in adulthood.
from environmental stimuli in utero.
from genetic alterations.
a, b, and c
Ans: B
Difficulty: 2
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39.
A)
B)
C)
D)
E)
Quantitative traits can be distinguished by:
being measurable.
being influenced by multiple genes.
not having genetic causes.
a and c
a and b
Ans: E
Difficulty: 1
40.
A)
B)
C)
D)
E)
Incomplete penetrance:
can vary from trait to trait.
is observed when the mutant genotype does not result in a mutant phenotype.
is only observed for late-onset diseases.
a and b
a and c
Ans: D
Difficulty: 3
41. If the chance a person being polymorphic for a particular microsatellite is 50%, what is
the chance that a person is polymorphic for four unlinked microsatellite loci?
A) 75%
B) 50%
C) 25%
D) 6.25%
Ans: D
Difficulty: 4
42.
A)
B)
C)
D)
SNP is the acronym for:
simple Northern probe.
single nucleotide polymorphism.
sample in situ probe.
simple nucleotide probe.
Ans: B
Difficulty: 1
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43. Below are several steps involved in Northern blots. From the choices available, pick the
order of steps that would be successful.
1. Blot the RNA from the gel to a filter.
2. Purify the RNA.
3. Separate the RNA by size in an electrical field in an agarose gel.
4. Expose the filter to a labeled probe to allow hybridization.
5. Develop the film.
6. Perform autoradiography.
A) Order 1, 2, 3, 4, 5, 6
B) Order 2, 3, 6, 4, 1, 5
C) Order 2, 3, 1, 4, 6, 5
D) Order 2, 3, 4, 1, 6, 5
Ans: C
Difficulty: 4
44.
A)
B)
C)
D)
E)
Predisposition to breast cancer results from mutations:
in multiple genes.
in BRCA1 that show 50% penetrance.
and from environmental causes.
a and b
a and c
Ans: D
Difficulty: 3
45.
A)
B)
C)
D)
E)
Identification of candidate genes:
can use a possible tissue specificity of expression.
can use evolutionary conservation of coding sequences.
can use short open reading frames.
a and b
a and c
Ans: D
Difficulty: 2
46.
A)
B)
C)
D)
E)
A transgene:
can be used to create new mutant organisms.
is a piece of foreign DNA that is inserted into the genome of an organism.
can be used to determine if a candidate gene is responsible for a disease phenotype.
a, b and c
a and c
Ans: D
Difficulty: 4
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47.
A)
B)
C)
D)
E)
The sequence of DNA is useful for:
finding differences between individuals.
finding information about protein function.
finding protein motifs.
duplicated genes.
all of the above
Ans: E
Difficulty: 3
48.
A)
B)
C)
D)
E)
F)
To find a gene that is responsible for a mutant or disease phenotype, the researcher will:
sequence the entire contig.
use Northern blots to find tissue-specific gene expression.
pick out regions of conserved sequence by hybridization.
look for mutations.
a, b, and c
b, c, and d
Ans: F
Difficulty: 3
49. Mapping a disease gene requires:
A) large families with DNA and pedigrees.
B) large numbers of mapped physical markers with complete genomic coverage and small
families with DNA and pedigrees.
C) small numbers of mapped markers and small families with DNA and pedigrees.
D) a or b
E) a or c
Ans: D
Difficulty: 2
50. If a human disease gene is within 5 cM of a physical marker, then it is approximately
within:
A) 5 kb
B) 50 kb
C) 5,000 kb
D) 50,000 kb
Ans: C
Difficulty: 4
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51.
A)
B)
C)
D)
E)
If a gene is thought to be a possible disease gene, one can:
sequence alleles from affected and unaffected family members.
examine the expression pattern of the gene.
make a transgenic mouse, if an appropriate mouse mutation is known.
all of the above
a and c
Ans: D
Difficulty: 3
52. Thalidomide was a common treatment for morning sickness in the 1950s. Children born
to mothers given this drug showed the phenotypes of a genetic disease known as
phocomelia, which involves shortened limbs. This may represent:
A) incomplete dominance.
B) genetic heterogeneity.
C) penetrance.
D) phenocopy.
Ans: D
Difficulty: 2
Matching
Match the terms with the definition that best fits.
a) allele
b) DNA polymorphism
c) anonymous locus
d) microsatellite
e) minisatellite
f) transgene
g) phenocopy
h) QTL
i) haplotype
j) linkage disequilibruim
53. ______ the existence of two or more genetically different classes in the same
interbreeding population.
Ans: b
Difficulty: 1
54. ______ a large DNA element composed of numerous repeats of a 10-40 base pair
segment.
Ans: e
Difficulty: 1
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55. ______ loci that control the expression of continuous traits.
Ans: h
Difficulty: 1
56. ______ the non-random distribution into the gametes of a population of the alleles of
genes that reside on the same chromosome.
Ans: j
Difficulty: 2
57. ______ A segment of DNA of unknown gene content that has been localized to a
specific site on a chromosome.
Ans: c
Difficulty: 1
58. ______ specific combination of linked alleles in a cluster of related genes.
Ans: i
Difficulty: 1
59. ______ any piece of DNA that has been experimentally inserted into an organism while
in the embryonic or germ cell stage.
Ans: f
Difficulty: 1
60. ______ alternative form of a single gene.
Ans: a
Difficulty: 1
61. ______ a non-heritable change in phenotype arising from environmental agents that
mimic the effects of a mutation in a gene.
Ans: g
Difficulty: 1
62. ______ DNA element composed of 15-100 tandem repeats of 1- 2- or 3-base
sequences.
Ans: d
Difficulty: 1
True or False
63. If a couple has a child who suffers from cystic fibrosis both parents must be a carriers.
Ans: True
Difficulty: 1
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64. Modern geneticists define an allele as any DNA site difference among genomes.
Ans: True
Difficulty: 3
65. If DNA is isolated from two healthy individuals, it is very likely that their DNA
sequence will be identical.
Ans: False
Difficulty: 2
66. All DNA sequence changes in the Cf gene lead to the disease called cystic fibrosis.
Ans: False
Difficulty: 3
67. Two members of homologous chromosomes from one individual show less sequence
differences than two of the same homologous chromosomes from two individuals.
Ans: False
Difficulty: 4
68. Microsatellites tend to be highly conserved, that is, once made they stay the same.
Ans: False
Difficulty: 2
69. DNA polymerase stutter is a main source of variation in microsatellites.
Ans: True
Difficulty: 4
70. The genetic role of minisatellites is well known.
Ans: False
Difficulty: 1
71. Misalignment during synapsis is a source of additional number of repeats in
minisatellites.
Ans: True
Difficulty: 3
72. The material deleted from one homologous chromosome can be material for duplication
in a homologous chromosome.
Ans: True
Difficulty: 1
73. Restriction sites refer to a specific DNA sequence recognized by a specific
endonuclease.
Ans: True
Difficulty: 1
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74. DNA fingerprinting established that Anna Anderson was the same as Grand Duchess
Anastasia.
Ans: False
Difficulty: 1
75. The DNA fingerprints of monozygotic twins are identical.
Ans: True
Difficulty: 2
76. A gene is simply a coding locus.
Ans: True
Difficulty: 2
77. Sequence variation is about 1 per 1000 bases for any two individuals.
Ans: True
Difficulty: 2
78. Nearly all SNPs are biallelic.
Ans: True
Difficulty: 1
79. DNA fingerprints identify polymorphisms in microsatellites and can be used to identify
family relationships between old skeletal material and living individuals.
Ans: True
Difficulty: 2
80. LOD score analysis is a statistical approach used to discover whether an unknown locus
is linked to a marker locus of known chromosomal location.
Ans: True
Difficulty: 2
81. QTL is the acronym for qualitative trait loci.
Ans: True
Difficulty: 2
82. Haplotype association in humans allows high-resolution gene mapping.
Ans: True
Difficulty: 2
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Short Answer
83. The parents of the two available embryos, one CfCf and the other Cfcf, chose to have
both placed in the womb. Using the carrier embryo increased their chance of having a
child, but they were willing to pass on a harmful allele to satisfy their own desire to
procreate. What would you have done in their place?
Ans: As a person familiar with genetic disease, I would have used the CfCf embryo,
only. As a layperson I would have done what the parents did in the textbook case
study.
Difficulty: 2
84. Compare and contrast the definition of an allele by Mendel, Morgan and other classical
geneticists to the definition offered by current geneticists.
Ans: Mendel and Morgan identified the existence of alleles if there were two or more
phenotypes associated with a gene. Current geneticists equipped with molecular
genetic tools define an allele as any DNA sequence difference between the DNA
in homologous chromosomes.
Difficulty: 2
85. Define a locus in a classic sense and define it in a modern sense. How are the two
definitions similar and different?
Ans: In the Mendel, Morgan or classic sense, a coding gene and its allele(s) were
associated with a location in a chromosome (a locus or prular loci). In current,
modern, use, a locus is any place in the genome where there is a base difference
between DNA of homologous chromosomes.
Difficulty: 2
86. If the recognition sequence for EcoR1 is 3 kb, 5 kb and 12 kb from the beginning of a
cloned fragment, what DNA fragments would be expected and what kind of probe might
be most useful?
Ans: Expected fragments would be 2 and 7 kb. A probe has complementary to flanking
the 5 kb recognition site.
Difficulty: 2
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Experimental Design and Interpretation of Data
A pure-breeding tomato with large fruit size (100 grams) is crossed to a pure-breeding tomato
with small fruit size (20 grams). The F1 generation has intermediate sized fruit (60 grams). A
plant from the F1 generation is crossed to the parent with small fruit size. The following data is
collected among the progeny of this cross.
87. What type of inheritance pattern do these data suggests?
Ans: quantitative trait loci
Difficulty: 2
88. Assume that there are equally contributing loci that produce this phenotype, how many
loci are likely to be involved?
Ans: 4
Difficulty: 4
89. How many different genotypes would be found among the plants that produce 30-gram
tomatoes?
Ans: 4
Difficulty: 4
90. How many different genotypes would be found among the plants that produce 40-gram
tomatoes?
Ans: 6
Difficulty: 4
91. If two F1 plants were crossed to each other and the fruit sizes among the F2 progeny
were examined, how many phenotypic classes would be observed?
Ans: 9
Difficulty: 4
92. If two F1 plants were crossed to each other and the fruit sizes among the F2 progeny
were examined, what fraction of the plants would produce fruits of 100 grams?
Ans: 1/64
Difficulty: 4
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93. How many alleles are involved in the determination of fruit size based on these parents?
Ans: 8
Difficulty: 4
Allele specific oligonucleotides (ASO) can be used to determine the different alleles present in a
DNA sample. Single sperm, which have completed meiosis, can be used for a polymerase chain
reaction (PCR). The amplified DNA is then spotted to filters and hybridized with probes that
recognize single nucleotide differences. Four primers (called A, B, D, and E) were used to
amplify DNA samples and ASO probes were used to determine the allele present (Either allele 1
or 2). X indicates the allele is present and – indicates the allele is not present.
94. Which loci are heterozygous?
Ans: A, D, E
Difficulty: 4
95. Which loci are linked?
Ans: A, D, E
Difficulty: 4
96. What genotypes are likely to have been contributed by this male's parents?
Ans: A1 B1 D1 E2 and A2 B1 D2 E1
Difficulty: 4
97. What is an estimate of the map distance between the three pairs of linked genes?
Ans: A-D = 25.3 cM, A-E = 10.6 cM, D-E = 35.9 cM
Difficulty: 3
98. What feature would distinguish a Y-linked gene if you used PCR-amplified ASO
markers in sperm?
Ans: Allele in only 1/2 of the sperm
Difficulty: 3
99. What feature would distinguish an X-linked gene if you used PCR-amplified ASO
markers in sperm?
Ans: Allele in only 1/2 of the sperm
Difficulty: 3
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Quantitative trait loci can be examined using pure-breeding parents and measuring a particular
trait. If each allele makes an equal contribution to the phenotype, then the number of loci can be
discerned. Bristle length in Drosophila behaves as a quantitative trait. If one parent has bristles
of 30 nm and a second fly has bristles of 10 nm, then the F1 will have bristles of 20 nm. If the
F1 flies are crossed to produce the F2 generation, the following classes of flies are observed.
Number of F2 Flies
Length of bristles
10
10
40
15
60
20
40
25
10
30
100. How many different genotypes would be found among the flies with 10 nm bristles?
Ans: 1
Difficulty: 4
101. How many different genotypes would be found among the flies with 30 nm bristles?
Ans: 1
Difficulty: 4
102. How many different genotypes would be found among the flies with 15 or 25 nm
bristles?
Ans: 2
Difficulty: 4
103. How many loci are affecting this trait?
Ans: 2
Difficulty: 4
104. If one wanted to find a physical marker that was linked to genes affecting bristle length,
which flies would be most useful?
Ans: 10 nm or 30 nm
Difficulty: 4
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