Deck 11: Analyzing Genomic Variation

Question 1

Allele-specific oligonucleotides (ASO)for the normal and disease alleles of a gene are in one section of a microarray.The disease is a recessive trait.If a probe made from an individual's genomic DNA hybridizes with both ASOs, what can be inferred about the individual?

A)The individual has two normal alleles.
B)The individual has the disease.
C)50% of the individual's children are expected to be carriers.
D)One of the individual's parents has the disease.

Answer 1

C

Question 2

Simple sequence repeats are

A)found only in coding regions of genes.
B)sequences of 1 to 10 base pairs repeated a variable number of times in tandem.
C)sequences that are 10 base pairs long or longer and found in several locations in the genome.
D)members of a gene family.

Answer 2

B

Question 3

The most common mutant allele of the PAH gene, which is responsible for the metabolic disorder PKU, has a SNP in the splice donor site of one intron.What is the simplest way to detect this allele?

A)PCR using genomic DNA as template and two primers, one on either side of the SNP, followed by gel electrophoresis
B)PCR using genomic DNA as template and two primers, one complementary to the region containing the SNP, followed by gel electrophoresis
C)PCR using two primers, one on either side of the SNP, followed by sequencing the PCR products
D)Direct exome sequencing using a microarray
E)Whole-genome sequencing

Answer 3

C

Question 4

Fragile X syndrome is caused by expansion of a trinucleotide repeat in the 5′ UTR of the FMR-1 gene.What is the simplest way to detect this expansion?

A)PCR using genomic DNA as template and two primers that are complementary to repeats on either side of the expansion, followed by gel electrophoresis
B)PCR using genomic DNA as template and two primers, one complementary to the repeat region and the other complementary to unique sequence, followed by gel electrophoresis
C)PCR using two primers that are complementary to unique sequences on either side of the repeat region, followed by sequencing the PCR products
D)Direct exome sequencing using a microarray
E)Whole-genome sequencing

Question 5

Which is an example of a SNP? (Select all that apply. )

A)A single base near the neurofibromatosis gene can be a G or a T; phenotype is not affected.
B)A single base change in the gene for β globin changes an amino acid and results in sickle cell anemia.
C)Individuals with Huntington disease have more trinucleotide repeats in the coding region of the HD gene than normal individuals.
D)The most common cystic fibrosis allele has a deletion of three base pairs in the coding region of the CFTR gene.

Question 6

Given that an individual is a compound heterozygote at the CFTR locus, the gene that causes cystic fibrosis, what can be inferred?

A)If the individual has children, all the children will have cystic fibrosis.
B)At least one of the individual's parents had cystic fibrosis.
C)The individual is a carrier for cystic fibrosis, but does not have the disease.
D)A drug that effectively treats one allele may not treat the other.

Question 7

Examine this pedigree that shows segregation of Huntington disease and the DNA marker G8.What was the most likely genotype of individual V-3 at the DNA marker?

A)BC
B)AB
C)CC
D)AC
E)All of the possible genotypes are equally likely.

Question 8

What mechanisms contribute to the formation of deletions and insertions? (Select all that apply. )

A)Repair of double-strand breaks in DNA
B)Errors in DNA replication
C)Unequal crossing-over due to mispairing of homologs
D)Repair of thymine dimers in DNA

Question 9

Which are limitations of preimplantation embryo diagnosis? (Select all that apply. )

A)The technique is technologically complex and expensive.
B)Only certain well-defined genetic diseases can be tested.
C)The test increases the rate of twin births.
D)Removal of one cell from an eight-cell embryo results in permanent damage to the embryo.

Question 10

Which statement about SNPs in the human genome is true?

A)Most SNPs have an effect on phenotype.
B)Any two human genome copies will have on average 3 million single nucleotide polymorphisms.
C)SNPs refer only to deletions or insertions, not base substitutions.
D)Most SNPs are located in the introns of genes, and thus effect phenotype.

Question 11

Most polymorphisms do not result in a phenotypic difference because they are typically

A)nonsense mutations.
B)either missense or neutral mutations.
C)either silent mutations or are in non-coding regions.
D)either missense mutations or are in promoter regions.

Question 12

Positional cloning depends on knowing what?

A)the function of a gene
B)the expression pattern of a gene
C)the map location of markers that are linked to a gene
D)the sequence of a gene.

Question 13

If a single DNA molecule is amplified by PCR, how many DNA molecules will exist after FIVE cycles?

A)6
B)8
C)10
D)32
E)64

Question 14

If the 13 CODIS SSR loci are genotyped, why does each person (except identical twins)have a unique combination of SSR alleles?

A)Each SSR locus has many alleles, each with a different number of repeats.
B)SSRs have a very low mutation rate in individuals.
C)SSR inheritance follows Mendel's law of segregation.
D)Mitotic recombination results in new combinations of SSRs in different parts of an individual's body.

Question 15

How many bases do deletion-insertion polymorphisms (DIPs)most frequently involve?

A)1-2
B)multiples of 3
C)10-100
D)more than 100

Question 16

Simple sequence repeat loci are highly variable because of what process?

A)repair of double strand breaks that result from exposure to X-rays
B)exposure to DNA damaging chemicals found in food and water
C)the formation of thymine dimers by ultraviolet light
D)slipped mispairing during DNA replication

Question 17

Which is the most common type of DNA polymorphism?

A)single nucleotide polymorphism
B)deletion/insertion polymorphism
C)simple sequence repeat
D)copy number variant

Question 18

Which does a successful PCR require?

A)at least 100 starting DNA template molecules
B)some sequence information about the region to be amplified
C)a cloned cDNA of the region to be amplified
D)a double-stranded DNA template of at least 100 kb to amplify
E)an undamaged DNA template with intact chromosomes

Question 19

Which are typically used for positional cloning of a disease gene in humans? (Select all that apply. )

A)analysis of several human pedigrees in which the disease is segregating
B)genotyping of diseased and healthy individuals at millions of anonymous polymorphisms using microarrays
C)sequencing candidate genes
D)a multigenerational selective breeding program

Question 20

The classical form of the metabolic disease phenylketonuria is caused by a mutation in the gene encoding the enzyme phenylalanine hydroxylase (PAH), which converts phenylalanine to tyrosine.A variant form of phenylketonuria is caused by a mutation in a separate gene that encodes a different enzyme involved in the synthesis of a cofactor needed for PAH to function.Which of the following phenomena is illustrated by these two forms of phenylketonuria?

A)Allelic heterogeneity
B)Compound heterozygosity
C)Locus heterogeneity
D)Anonymous polymorphism

Question 21

How can databases of variants be used to help pinpoint a disease-causing mutation? (Select all that apply. )

A)Polymorphisms found in individuals that do not have the syndrome can be eliminated from consideration.
B)Common polymorphisms are unlikely to cause a rare disease and they can be eliminated from consideration.
C)Some amino acids are conserved in genes across species; mutations in conserved amino acids are not likely to cause disease.
D)Mutations that occur between genes are most likely to cause a genetic disease.

Question 22

What additional data would increase your confidence that the gene of interest and the DNA marker are linked? (Select all that apply. )

A)Analysis of another mating from the same pedigree that produced 4 parental and 4 recombinant offspring.
B)Analysis of a mating from a different pedigree that produced 4 parental and 4 recombinant offspring.
C)Analysis of a mating from a different pedigree that produced 6 parental and 2 recombinant offspring.
D)Analysis of another mating from the same pedigree that produced 6 parental and 2 recombinant offspring.

Question 23

What is the name of the process for removing amniotic fluid from a pregnant mother to obtain fetal cells for genetic testing?

A)amniocentesis
B)polymerase chain reaction
C)preimplantation genetic diagnosis
D)in vitro fertilization

Question 24

In 2008, Margaret Binkele was murdered in her Georgia home.The number of repeats at three CODIS simple sequence repeat (SSR)loci were determined using crime scene samples and blood from three suspects.The results are summarized in the table.
Genotypes at three SSR loci
$$\begin{array} { | c | c | c | c | c | } \hline & \text { Crime scerie sarmple } & \text { Suspect 1 } & \text { Suspect 2 } & \text { Suspect 3 } \\\hline \text { SSR locus 1 } & 10,10 & { 8 } , 10 & 6,7 & 10,10 \\\hline \text { SSR locus 2 } & 11,11 & 11,11 & 9,15 & 10,12 \\\hline \text { SSR locus 3 } & 6,9 & 6,7 & 6,9 & 6,9 \\\hline\end{array}$$

-According to the data, the crime scene sample matches the sample from which suspect?

A)Suspect 1
B)Suspect 2
C)Suspect 3
D)None of the suspects is a match

Question 25

Which is a challenge of using pedigrees for positional cloning?

A)Some matings may not be informative.
B)Recombination occurs during meiosis.
C)Many individuals in a pedigree are unaffected.
D)Pedigrees are not based on DNA sequences.

Question 26

Identifying candidates for a disease gene by positional cloning depends on distinguishing DNA markers that are close to the disease gene from markers that are far away.When the disease gene is close to a marker, there will be

A)a high number of mutations in the intervening DNA.
B)a low rate of recombination between the disease gene and the marker.
C)many alleles at the marker locus.
D)a high chance of locus heterogeneity.

Question 27

In 2013, a man was arrested for transporting 400 pounds of marijuana across state lines.His DNA was tested, entered into the CODIS database, and found to match the crime scene sample in the Margaret Binkele case.What additional evidence would increase your confidence that the man arrested for transporting marijuana murdered Margaret Binkele? (Select all that apply. )

A)A receipt that showed the man used his credit card in Texas on the night of the murder
B)The genotype at additional SSR loci that show a match at seven and a mismatch at three loci.
C)Discovery of the man's fingerprints on the murder weapon
D)A match between his blood and the crime scene sample at more than three SSR loci

Question 28

Linkage between a gene of interest and a DNA marker is being studied. A mating results in 6 parental and 3 recombinant offspring


-What is the maximum Lod score for this mating?

A)0.22
B)1.1
C)6.3
D)11

Question 29

How can microarrays differentiate between a wild-type allele and a disease allele that differ at only one nucleotide?

A)The DNA sequences of both alleles are determined.
B)Oligonucleotides hybridize with the two alleles differently.
C)Polymerase chain reaction primers amplify DNA from one allele, but not the other.
D)Microarrays are not capable of detecting a difference between those alleles.

Question 30

Linkage between a gene of interest and a DNA marker is being studied. A mating results in 19 parental and 1 recombinant offspring.

-The results of this mating are sufficient to conclude with confidence that the gene of interest and the DNA marker are linked.

Question 31

You are studying a disease that is known to be caused by a single nucleotide change in a single gene, although the effect this change ultimately has on the protein's structure and function is unknown.You have DNA samples from multiple patients that you suspect of having this disease.What is the most efficient way to test the samples for the relevant mutation?

A)Preimplantation genetic diagnosis
B)PCR amplification followed by Sanger DNA sequencing
C)PCR amplification followed by gel electrophoresis
D)High-throughput exome sequencing
E)High-throughput genome sequencing

Question 32

Linkage between a gene of interest and a DNA marker is being studied. A mating results in 19 parental and 1 recombinant offspring.

-What is the maximum Lod score for linkage at this locus?

A)0.22
B)1.1
C)6.3
D)11

Question 33

Herceptin is a drug that is given to treat certain breast cancers.However, it is most effective on tumors that are overexpressing the gene HER2.Which of the following strategies would be best for determining whether Herceptin would be effective in a given patient?

A)Sequence DNA from the patient's sperm or eggs to determine whether the patient's germ cells contain gain-of-function mutations in HER2, and treat with Herceptin only if they do.
B)Determine the patient's HER2 sequence and compare it to a database of known HER2 mutations to determine whether the overexpression allele is present; if the overexpression allele is present, give Herceptin .
C)Determine the patient's HER2 sequence and compare it to a database of known HER2 mutations to confirm that the patient has a mutation in the gene; give Herceptin if any mutation is found.
D)Perform microarray analysis to determine the location of the patient's HER2 gene and give Herceptin if the HER2 gene is not in the normal location.

Question 34

What technique can help identify a disease gene quickly by narrowing the focus?

A)Compare the genome sequences of different species to identify conserved amino acids
B)Filter the results to include only common polymorphisms
C)Determine genotypes of parents and children at all SSR loci
D)Use microarrays to identify silent mutations

Question 35

Which polymorphism is most likely to affect an individual's phenotype?

A)An SNP in an intron of a protein-coding gene
B)An SSR within a telomeric sequence
C)A DIP in an intragenic region between genes
D)An SNP in the start codon of a protein-coding gene

Question 36

Which is part of a DNA sequencing technique that is useful for high-throughput sequencing, but is not part of Sanger DNA sequencing?

A)Using dideoxynucleotides as chain terminators
B)Separating DNA by size using gel electrophoresis
C)Hybridization between the template and a primer
D)Removal of a chemical group that blocks the 3′ end of the new DNA strand
E)Labeling deoxynucleotides with fluorescent tags

Question 37

Linkage between a gene of interest and a DNA marker is being studied. A mating results in 6 parental and 3 recombinant offspring


-The results of this mating are sufficient to conclude with confidence that the gene of interest and the DNA marker are linked.

Question 38

In the United States, most newborns undergo a screening test for up to 60 genetic disorders.A few drops of blood is taken from each baby and the levels of various blood components are determined.The screening identifies babies who might have a genetic disorder, but is not diagnostic.Further testing is required if the screen shows a blood component is out of the normal range.Which of the following technologies could potentially be a low-cost replacement for the current newborn screening and would directly test most babies for the presence of many genetic disorders?

A)PCR to amplify the PKU gene
B)exome sequencing and comparison with known mutations in databases
C)DNA fingerprinting using CODIS SSRs
D)preimplantation genetic diagnosis