Genetics problems - Đề thi môn sinh học có hướng dẫn chi tiết

Problems Section 1
1. Chromosomal disorders do not manifest disease until late in life.
A. True
B. False

2. Genetic counselors currently do the majority of genetic counseling for patients
A. true
B. false
3. 6-mercaptopurine has been used successfullly to treat acute lymphocytic leukemia and inflammatory
diseases, like Crohn's syndrome. However, 1 in 300 individuals have a toxic reaction. There has been
signficant discussion about getting the FDA to require appropriate labeling. Why is that?
A. 6-mercaptopurine taken with certain foods is toxic
B. Individuals with sickle cell anemia cannot take 6-mercaptopurine
C. Patients with homozygous mutations in the TPMT gene have a toxic reaction to 6-
mercaptopurine
4. A patient is found to have a mutation for HNPCC, hereditary non-polyposis colon cancer and based on
his pedigree, it is inherited, i.e it is found in other family members. How do you counsel him to deal
with his genetic disease?
A. Encourage him to tell his family
B. Contact all of his first degree relatives and advise them to be tested
C. Treat the disease and forget about the genetics
Problems Section 2
1. How would the genetic content of the somatic cells of individual A, who is the product of a meiotic
nondisjunctional event, differ from that of B, who experienced a mitotic error early in development? Avoid
consideration of exceptional cases.
a. A’s cells would be genetically heterogeneous; B’s cells would be genetically homogeneous.
b. A’s cells would be genetically homogeneous; B’s cells would be genetically heterogeneous.
c. A’s and B’s cells would be genetically heterogeneous.
d. A’s and B’s cells would be genetically homogeneous.
2. How may these patients differ clinically, assuming the same autosome is involved in each case?
a. A and B would develop clinical symptoms of similar intensity.

b. A would be clinically affected, but B would be normal.
c. A would be clinically affected. The degree of abnormality in B would depend upon the proportion of
aneuploid cells present.
d. B would be clinically affected, but A would be normal.
3. A man and woman have a daughter with Turner syndrome (45,X). The glucose-6-phosphate dehydrogenase
genotypes of this family are:
Father: G6PD
A
Mother: G6PD
B
G6PD
B
Daughter: G6PD
A
G6PD is X-linked. During which stage(s) of meiosis could nondisjunction have occurred?
a. Anaphase I in the father c. Anaphase II in the father
b. Anaphase I in the mother d. Anaphase II in the mother
4. Two of the following techniques have proven useful in accurately identifying each chromosome. Select
the appropriate methods.
a. Autoradiography
b. G-banding
c. FISH
d. C-banding
5. Schematically outline meiosis in a male using one pair of autosomal alleles (A and a) and the sex
chromosomes (X and Y). If a encodes an abnormal protein, predict the proportion of normal and
anomalous gametes.
a. ½ A,X ; ½ a,Y c. ½ a,X; ½ A,Y
b. ¼ A,X ; ¼ a,X; ¼ A,Y ; ¼ a,Y d. ¼ A,X ; ¼ a,X; ½ A,Y
6. A female infant has trisomy (triplication) of chromosome 10. How would you express her karyotype
according to standard nomenclature? Assume there are no other abnormalities in her karyotype.

a. 46,XY,+10 c. 46,XX; 47,XX,+10
b. 47,XY,+10; 46,XY d. 47,XX,+10
7. Anaphase lag refers to loss of a chromosome during meiosis or mitosis due to failure to migrate to the proper
pole of the dividing cell. Which of the following children most likely originated following mitotic
anaphase lag? Semicolons separate karyotypes of different cell lines.
a. 46,XX ; 45,XX,-21 c. 46,XX
b. 47,XX,+21 ; 45,XX,-21 d. 47,XX,+21
8.You have received a report from a clinical cytogenetics lab stating that one of your patients has the karyotype:
46,XX,del(18)(q12). What does this mean?
a. Male with a deletion of the short arm of 18 distal to band 12
b. Female with a deletion of the short arm of 18 distal to band 12
c. Male with a deletion of the long arm of 18 distal to band 12
d. Female with a deletion of the long arm of 18 distal to band 12
9. If this patient was fertile, how would you counsel the patient relevant to future children? Assume that there
is no mosaicism for the alteration specified in (15), and that the alteration is present in the gametic cell line.
a. The defect is sporadic and will not recur.
b. About half of the male children only will inherit the same alteration.
c. About half of the children, regardless of sex, will inherit the alteration.
d. All of the children will inherit the alteration.
Problems Section 3
1. A patient with a rare inherited syndrome was found to have 10% of normal enzyme “X” activity. Isolation
and characterization of the erythrocyte form of the enzyme indicated that the mutant protein differed from its
normal counterpart by a single amino acid substitution. The syndrome
a. is due to a regulatory gene mutation.
b. is caused by the presence of an inhibitor.
c. is the result of an exonic base substitution.
d. resulted from a failure in hormonal induction of gene activity.
2. Based upon your knowledge of biochemistry and genetics, which of the following observations would
indicate that a hormone was specifically inducing enzyme “A” activity?
a. An increase in enzyme “A” activity

b. An increase in mRNA, rRNA, tRNA, and enzyme “A” activity
c. An increase in enzyme “A” mRNA and enzyme “A” activity
d. Accumulation of the hormone in the nucleus and the changes observed in 2b.
Questions 3–10: Match the following with their appropriate functions in the cell.
3. rRNA a. Initiates protein synthesis
4. Polysome b. Shuttles amino acids to
ribosomes
5. Promoter c. Pool including nuclear mRNA
precursors
6. HnRNA d. Contains DNA elements influencing transcription of a gene
7. tRNA e. Aggregate of mRNA and
ribosomes
8. Methionyl tRNA f. Structural component of
ribosomes
9. UAA, UAG, UGA g. Orders amino acid sequences of
proteins
10. mRNA h. Chain terminators
11. Outline transcription and translation using the appropriate base abbreviations and three code words. Start
with DNA: AGCTCCAAA and use the table of the genetic code in your biochemistry textbook.
12. HbZ has an altered β-chain. The amino acid sequence is normal from residue 1 to residue 46 and from
residue 70 to the end of the chain. Residues 47–69 do not match sequences from any known normal
hemoglobin chains. How may this mutant hemoglobin arise?
a. Substitution of a base in codon 47
b. Insertion of a base into codon 46
c. Deletion of a base from codon 47
d. Insertion of a base into codon 47 and deletion of a base from codon 69
e. Deletion of a base from codon 47 and insertion of a base into codon 69
13. Arylsulfatase A is deficient in patients afflicted with the progressive neurological disease, metachromatic
leukodystrophy. You have successfully purified this enzyme and have prepared a specific antibody against
it. You find that immunotitration of extracts of cells cultured from the patient’s skin demonstrates very low

levels of arylsulfatase A protein. Mutations involving which of the following DNA sequences would
explain the low levels of arylsulfatase A protein in this patient?
a. The promoter of the arylsulfatase A transcriptional unit.
b. An exon of the arylsulfatase A transcriptional unit.
c. A gene affecting the intracellular distribution of arylsulfatase A.
d. An exon-intron splice junction of the arylsulfatase A transcriptional unit.
14. Which of the following structures appear to be physical manifestations of the inactive X chromosome in
interphase nuclei?
a. Barr body c. Y body
b. Nucleolus d. Sex vesicle
15. The genetic code consists of triplets derived from four different bases. The “degeneracy” of the code may generally be
attributed to variation in
a. the first nucleotide of the triplet.
b. the second nucleotide of the triplet.
c. the third nucleotide of the triplet.
d. all three nucleotides.
16.
A simple human gene is illustrated in the above diagram. This gene is transcribed from left to right. A
mutation at the position of the arrow (asterisk = ATG) would most likely affect
a. efficiency of transcription. d. stability of the mRNA.
b. accuracy of transcription. e. initiation of mRNA translation.
c. processing of the pre-mRNA.
Problems Section 4
1. Given that base analogs result in the replacement of existing bases in DNA, predict the effect of such a
substitution at the molecular level.
a. A new amino acid may be inserted at the corresponding point in the
polypeptide
b. Chain termination may occur such that an incomplete polypeptide is formed.
c. No change may result.
d. A shift in the reading frame may occur.

2. Why have most attempts to improve the fitness of organisms through induced mutations failed?
a. Mutagens are typically nonselective in their points of action.
b. Most mutations are harmful.
c. Inappropriate experimental systems have been used.
d. Mammals are highly sensitive to these mutagens.
Questions 3–7: Match the following mutagens with their nuclear effects.
3. X-rays a. Thymine dimers
4. Ultraviolet light b. Base substitution
5. Nitrogen mustards c. Alkylation
6. Base analogs d. Ionizations
7. Nitrous oxide e. Intercalation
Question 8: True or False

8. The degree of radiation damage is greater in mitotically or meiotically dividing tissue than in nondividing
tissue.
9. A mutant β-globin chain from a patient with hemolytic anemia contained 157 amino acids rather than the
normal 146. The amino acid sequence of the mutant β-globin chain was identical to the normal chain
through amino acid 135; however, the sequences after that point were markedly different. Describe the
mutation most likely responsible for this patient’s disease.
10. The following patterns are observed for a DNA polymorphism after digestion of genomic DNA with the
restriction enzyme Eco RI: in males, a fragment of either 9 or 11 kB; in females a fragment of either 9 or
11 kB or both. What is the likely origin of these patterns?
Problems Section 5
1. A woman with facioscapulohumeral muscular dystrophy (FMD), an autosomal dominant trait, is seeking
advice on having children. Her husband, who is 28 and normal, has an uncle with Huntington’s disease
(HD; autosomal dominant). His parents are normal, and both are over 50. Symptoms of Huntington’s
disease may appear from 12 to 65 years after birth; however, all HD members of his father’s kindred
developed signs during their thirties. HD and FMD are fully penetrant. What are the genetic risks for this
couple’s children?
a. 50% FMD, 50% HD d. 100% FMD, 0% HD

b. 50% FMD, 0% HD e. 50% FMD, 25% HD
c. 0% FMD, 50% HD
2. Tuberous sclerosis is characterized by adenoma sebaceum (facial rash across bridge of nose), epilepsy,
mental retardation, and risk for multiple tumors. The disease frequently causes early death, usually before
age 21. Although penetrance is close to 100%, the disease is quite variable in expression. The disease is
inherited as an autosomal dominant and affects about 1/10,000 persons. A normal woman with a slight
reddening across the bridge of her nose has one child with the severe disease. What is her risk for a second
affected child?
a. About 0 d. 50%
b. 10% e. 100%
c. 25%
3. Demonstration of allelism in humans is difficult. Assume that two traits are codominant. Which of the
following tests would be most helpful in suggesting they are determined by allelic genes?
a. Failure of a person with both traits to transmit both to the same child
b. Lack of occurrence of both traits in the same person
c. Lack of a doubly affected child among offspring of two parents, each of whom has only one of
the traits.
d. Absence of normal children from marriages of doubly affected individuals to normal individuals.
e. Both a and d above
Question 4: True or False

4. A normal ancestry indicates that a trait is not hereditary—even if two or more affected siblings are present in
a family.
5.Sickle cell trait describes individuals who are heterozygous for normal hemoglobin HbA and sickle cell
hemoglobin HbS, ie, they are HbS/HbA. Two people have sickle cell trait and marry. Predict the possible
phenotypes of their children and their frequencies. Note: sickle cell anemia occurs in HbS homozygotes.
a. 1/4 sickle cell trait, 1/2 sickle cell anemia, 1/4 normal
b. 1/2 normal, 1/2 sickle cell anemia
c. 1/2 sickle cell trait, 1/2 sickle cell anemia
d. 1/2 normal, 1/2 sickle cell trait

e. 1/4 normal, 1/2 sickle cell trait, 1/4 sickle cell anemia
6. Phenylketonuria is a disease resulting from lack of the enzyme, phenylalanine hydroxylase. The clinical
symptoms of mental and growth retardation, microcephaly, seizures, and eczema are limited to untreated
homozygotes. Heterozygotes have intermediate levels of enzyme activity in liver extracts. Select the
correct statement(s).
a. Phenylketonuria is a recessive disease.
b. Phenylketonuria is a dominant disease.
c. Phenylketonuria is a polygenic trait.
d. The effects of the normal allele are dominant to those of the abnormal allele.
e. Both a and d above
7.The genes encoding the variant chains in HbS and HbC are allelic. Homozygosity for either gene results in
anemia, with HbC disease being much less severe than sickle cell anemia. Heterozygosity for either allele
and the allele determining the normal chain in HbA results in a normal phenotype. What would you predict
for the β
S
β
C
heterozygote?
a. No disease
b. Anemia of intermediate severity with respect to sickle cell anemia and HbC disease
c. Mild problems like HbC disease
d. Sickle cell trait
e. This combination of alleles would be fatal
8.A syndrome characterized by multiple congenital malformations and mental retardation was observed to occur
twice in this kindred. What type of inheritance?
a. Autosomal dominant c. Autosomal codominant
b. Autosomal recessive d. Autosomal dominant, 2 loci
9. What type of inheritance is responsible for transmission of trait C in this pedigree:
a. Autosomal dominant c. Autosomal codominant
b. Autosomal recessive d. Autosomal dominant, 2 loci

10. A man has been working as an X-ray technician at a community hospital. He and his wife recently had a
baby born with cystic fibrosis, an autosomal recessive disease. The man has brought suit against the
hospital and radiologist, claiming that his occupational exposure to X-irradiation is responsible for the
disease in their child. He supports his claim by saying there is no history of cystic fibrosis in his nor his
wife’s families. As presiding judge in this case, how would you rule and why?
Problems Section 6
1. The GYPA blood group contains three common phenotypes: M, MN, and N. Calculate the frequencies of
the GYPA
M
and GYPA
N
alleles, if there are 600 M, 1,200 MN, and 200 N individuals in the population.
Let p = the frequency of GYPA
M
and q = the frequency of GYPA
N
.
a. p = 0.4, q = 0.6 d. p = 0.6, q = 0.4
b. p = 0.5, q = 0.5 e. none of the above
c. p = 0.65, q = 0.35
2. Which of the following diseases tend to be unequally distributed (more frequent in certain populations than in
others) among human populations?
a. G6PD-deficiency d. Cystic fibrosis
b. Tay-Sachs disease e. All of the above
c. Sickle cell anemia
3. What factors may account for your answer in (2)?
a. Large differences in mutation rates between populations
b. Selective advantage of the heterozygote
c. Genetic drift in small founder populations or inbred groups
d. Experimental error in determining gene frequencies

4. Trait A is an autosomal dominant exhibiting 80% penetrance. Twenty-four affected children out of one
million born to normal parents were observed over a period of 20 years at major hospitals in a western
country. What is the apparent mutation rate?
a. 3 x 10
-5
d. 1.2 x 10
-5
b. 1.5 x 10
-5
e. 1.9 x 10
-5
c. 2.4 x 10
-5
5. Do you feel your estimate in question 4 is biased?
a. No. The estimate is correct.
b. Yes, because of the possible lack of penetrance in the parents, some of the abnormal alleles were not
mutations. The estimate may be too high.
c. Yes, because of the selection of major hospitals only, a bias toward an overestimate or underestimate
may be present.
d. Yes, because of the lack of penetrance in the children, some of the mutations may have been missed.
The estimate may be too low.
6. A population has the following ABO blood group distribution: A = 4,900, B = 1,000, O = 4,000, AB = 100.
Calculate the frequencies of ABO
A
(= p), ABO
B
(=q), and ABO
O
(=r).
p q r

a. 0.32 0.05 0.63
b. 0.50 0.20 0.30
c. 1.00 0.20 1.00
d. 0.30 0.60 0.10
e. 0.49 0.11 0.40
7. Phenylketonuria occurs with a frequency of approximately 1/15,000 in Illinois (Illinois Department of
Public Health). What is the frequency of heterozygotes in this state?
a. 1/7,500 d. 1/62
b. 1/1,000 e. 1/25
c. 1/123
Question 8: True or False

8. Selection against the heterozygote will favor the more common allele.
9. Heterozygous advantage is believed to maintain stable polymorphisms in which the frequency of the rarer
allele exceeds 1%. Which of the following diseases may be maintained by stable polymorphisms?
a. Cystic fibrosis (aut. rec., 1/2,500)
b. PKU (aut. rec., 1/15,000)
c. Huntington's disease (aut. dom., 1/20,000)
d. G6PD-deficiency (X-linked rec., 1/10 males of Asian, African, or Mediterranean ancestry)
10. Neighboring Indian tribes in Utah have quite different ABO frequencies. Tribe 1 is 100% Type O, and
Tribe 2 is 95% Type A. Cultural barriers prevent marriage between the tribes, even though they are only a
few miles apart. What factor is most likely responsible for the difference in allele frequencies?
a. Selection c. Genetic drift
b. Mutation d. None of these
11. Given that Duchenne muscular dystrophy is an X-linked recessive illness, that the hemizygous males are
unable to reproduce, and that 1/3 of all X chromosomes are in males, calculate the frequency of this trait in
males if the mutation rate is 1/25,000. Assume this population is at equilibrium.
a. 1/75,000 c. 1/100,000
b. 3/25,000 d. 1/200,000
12. Suppose you are practicing where first cousin marriages are legally permitted. Two first cousins come to

you for counseling, since they intend to marry. Their common grandfather is known to be heterozygous for
an allele that causes severe mental retardation in homozygotes. What is the chance that their child will
inherit two copies of this allele, both derived from the grandfather?
a. 1/4 c. 1/16
b. 1/8 d. 1/64
13. What is the inbreeding coefficient for an aunt-nephew marriage?
a. 1/4 c. 1/16
b. 1/8 d. 1/32
14. How is this value interpreted?
a. It represents the proportion of heterozygous loci in a common ancestor (with respect to parents of
child) rendered homozygous in a child by descent.
b. It is the chance that an inbred child will inherit a deleterious dominant gene from an ancestor.
c. It is the chance that an inbred child will develop a recessive disease caused by an allele present in an
ancestor.
d. This is the chance that a given locus heterozygous in a common ancestor will be rendered homozygous
in a child by descent.
15. Genetic differences among races generally reflect
a. presence or absence of alleles in one race, but not another.
b. differences in relative frequencies of alleles among the races being compared.
c. the effects of migration, isolation, and divergent evolution.
d. the effects of diverse environments upon allele frequencies.
Problems Section 7
1. True or False: Maternal serum alpha fetoprotein levels are diagnostic for neural tube defect.
2.A woman and her husband are carriers for the autosomal recessive disorder Tay-Sachs disease, thus, both have
mutant HEX A genes and have requested first polar body diagnosis. PCR and DNA analysis have revealed
the presence of a normal HEXA allele in the polar body. How would this result be interpreted?
a. The oocyte also has the normal allele.
b. The Tay-Sachs allele is in the oocyte.
c. The oocyte contains both the normal and Tay-Sachs alleles.
d. HEXA alleles are absent from the oocyte.

Questions 3-9. Match the following screening methods with the disease they are designed to detect.
3. Method of obtaining fetal blood for karyotyping a. RH immune globulin
b. 10
th
week of pregnancy
4. Usual time at which amniocentesis is performed c. cordoentesis
d. mosaicisim
5. Increased level when fetus has a neural tube defect e. 16
th
week of pregnancy
f. alpha feto protein in materal serum
6. Contains fetal cells viable in culture g. aneuploidy
7. Risk increases with maternal age h. cystic hygroma
8. Usual time at which CVS is performed i. Chrorionic villus
9. Derived from extraembryonic tissue j. amniotic fluid
10. A maternal serum screen performed on a pregnant woman shows reduced MSAFP, reduced unconjugated
estriol and increased human chorionic gonadotrophin, you do which of the following:
a. suspect a neural tube defect and order an ultrasound
b. suspect down syndrome and order ultrasound to confirm age of the fetus, note the maternal age and
suggest amniocentesis
c. diagnose the fetus as having Edward’s syndrome
d. order additional screens like pregnancy associated plasma protein
Problem Section 8
1. Which of the following chromosomal aberrations is/are more frequently in abortice series than in liveborn
populations?
a. Sex-chromosomal trisomies c. X-monosomy
b. Triploids d. Trisomy 21
2. Laboratory studies have revealed the following groups of mothers. The mother’s karyotype is provided at
the left of the semicolon, and the baby’s at the right. A (/) separates karyotypes of two different cell lines in
the same person. Assume all mothers are under 30 years of age.

a. 46,XX ; 47,XY,+21
b. 45,XX,-14,-21,+t(14q21q) ; 46,XY,-14,+t(14q21q)
c. 45,XX,-21,-21,+t(21q21q) ; 46,XX,-21,+t(21q21q)
d. 46,XX (90%)/47,XX,+21 (10%) ; 47,XY,+21
Rank the mothers in order of increasing risk of recurrence of Down’s syndrome.
a. abcd
b. dabc
c. cbda
d. adbc
Questions 3: True or False

3. Young mothers with two Down’s syndrome children are victims of fate and need not worry about having a
third Down’s syndrome child until after age 40.
4. A man is a balanced carrier for a 13/14 Robertsonian translocation. Diagram the division figure that would be
observed at Metaphase I of meiotic division.
5. List the chromosome combinations of gametes derived from adjacent and alternate segregation in his cells.
6. True or False: This man has a slightly elevated risk for having a child affected with Patau syndrome.
Questions 7-11: Match the following karyotypes with their appropriate syndromes.
7. 47,XX,+21 a. Patau’s syndrome
b. Balanced translocation carrier
8. 47,XY,+13 c. Translocation Patau’s syndrome
9. 46,XX,5p- d. Turner’s syndrome
e. Edward’s syndrome
10. 46,XX,-14,+t(13q14q) f. Down’s syndrome
11. 45,XY,-14,-21,+t(14q21q) g. Cri-du-chat syndrome
h. Klinefelter’s syndrome
Problems Section 9
1. Which of the following chromosome errors would be the most benign relevant to their clinical
manifestations?
a. Even-numbered polyploids d. Autosomal trisomies

b. Odd-numbered polyploids e. Sex chromosomal trisomies
c. X-monosomy
2. Why did you select your answer to question 1?
a. Excessive genetic material is not as deleterious if present in even increments.
b. Chromosomes involved in autosomal trisomies are usually smaller than those participating in sex
chromosomal trisomies.
c. X-inactivation tends to diminish the effects of extra X chromosomes
d. The Y chromosome carries few active genes.
e. Deficiencies of chromosome material are less severe than excesses.
3. Which of the following chromosomal aberrations is/are more frequent in abortice series than in liveborn
populations?
a. Sex-chromosomal trisomies c. X-monosomy
b. Triploids d. Trisomy 21
Questions 6 : True or False

4. Maleness is determined by the ratio of Y to X chromosomes (Y/X > 1).
5. A 27-year-old woman in your care has rarely menstruated, has short stature, neck webbing, and pre-pubertal
breast development. She appears to have normal intelligence. She has been married for six years, but she
and her husband have been unable to have children. What is your provisional diagnosis?
a. Klinefelter’s syndrome d. Turner’s syndrome
b. 47,XYY e. 47,XXX
c. Down’s syndrome
6.Why are 46,XY* females infertile (Y* refers to a Y chromosome lacking SRY)?
7.Frequent recombination of genes in the pseudoautosomal regions of the X and Y chromosomes is believed to
occur during male meiosis. Rarely this recombination may include SRY, transferring the region to the X
chromosome. Predict the appearance of an individual inheriting such a recombinant X chromosome.
8. A gene, SHOX, encodes a DNA-binding protein that activates genes contributing to height. The gene is
located within the pseudoautosomal region of both the X and Y chromosomes. SHOX is not X-inactivated.
Why may Turner (45,X) women have short stature?
Problems Section 10

1.Activation of genes appears to be associated with
a. modification of chromosome structure.
b. interaction of steroid hormone-receptor complexes with promoters.
c. interaction of temporally- and spatially-specific transacting proteins with promoter elements.
d. interaction of peptide hormones with cyclic AMP-generating systems.
2.True or False for 2 and 3:
RNA polymerase only needs to find its promoter sequence in order to initiate transcription
3.The Hox genes are human-specific regulatory genes that encode DNA binding proteins.
For 4 –10, match the disorder with the gene that is mutated:
4.Rubenstein-Taybi syndrome-mental retardation a. HoxD13
Broad thumbs and toes, hirsuit, specific facies b. HoxA
5. Aniridia c. Sonic hedgehog
6. Type 2 Waardenburg syndrome d. Pax 3
7. Type 1 Waardenburg syndrome e. Pax 6
8. Type 3 Waardenburg syndrome f. Creb
9. Holoprosencephaly g. Pax 4
10. Synpolydactyly h. Mitf
11. Type 4 Waardenburg syndrome i. CBP
j. Sox10
k. EDN3
12. Waardenburg syndrome is an autosomal dominant condition that accounts for 1.4% of the cases
of congenital deafness. In addition to deafness, patients with this condition have atypical facies,
including lateral displacement of the inner canthi and partial albinism. A mother has Waardenburg
syndrome, her husband is unaffected, and they plan to have 3 children. What is the probability that one of the
three children will be affected?
a. 1/8
b. 1/4
c. 3/8
d. 1/3
e. 1/2

Problem Section 11
1.Which of the following are reasons to map genes?
a. The map position might suggest candidate genes that map to the same position
b. Although the identity of the gene causing disease is not precisely known, knowing the map position
might allow carrier detection or prenatal diagnosis by linked markers
c. comparison of the human and mouse map in their corresponding regions might point to possible animal
models for the disease.
2.Alternate forms of enzymes X and Y are respectively inherited as autosomal codominant traits. Several families
have been studied to determine whether these loci are linked. The cumulative Z scores were (Q=
recombination frequency):
Q Z Q Z
0 0.00 0.3 +4.25
0.1 +0.25 0.4 +0.45
0.2 +0.50 0.5 0.00

What would you conclude?
a. The loci are unlinked c. The loci are 30cM apart
b. The loci are 10cM apart d. X and Y appear to be determined by allelic genes
3. Consider the following pedigree:
What would you conclude regarding traits A and B?
a. The traits are most likely linked.
b. The traits are assorting independently.
c. The traits are allelic.
d. The traits are codominant.
4. Assuming the traits are linked, what is the most likely configuration in I–1?
a. The genes encoding traits A and B are cis.
b. The genes encoding traits A and B are trans.
5. Assuming the traits are linked, which individuals are recombinants?
a. II-1, II-2, II-4, III-1, III-4
b. II-3, III-2

c. II-1, II-4, III-3
d. II-2, III-3, III-4
e. There are insufficient data to determine recombinants.
6.The F8 gene encodes a clotting factor and is closely linked to G6PD, a second enzyme-encoding locus, on the
X chromosome. The daughter of a hemophiliac male (factor 8 deficiency) has two sons, one of whom has
hemophilia like his grandfather. The hemophiliac son is G6PD-A, while his normal brother is G6PD-B. The A
and B G6PD isozymes are inherited as X-linked codominant traits. Select the correct chromosomal arrays of the
F8 and G6PD alleles on the X chromosomes of the woman. A (/) separates genes on one chromosome from
those on its homolog. F8
+
= normal allele; F8
o
= hemophilia allele.
a. F8
+
G6PD
B
/F8
o
G6PD
A
c. F8
o
G6PD
B
/F8
+
G6PD
A
b. F8

+
G6PD
B
/F8
o
G6PD
B
d. F8
+
G6PD
A
/F8
o
G6PD
A
7. Treatment of DNA from members of a large kindred with the restriction enzyme, Hind III, produced four
different-sized DNA fragments which hybridized with a probe specific for a region of
chromosome 4 containing the Huntington’s disease (HD) gene or its normal allele. Members of the kindred
affected by Huntington’s disease are indicated by filled symbols. The combination of restriction fragments
containing the HD gene or its normal allele is presented below each symbol. The boy indicated by the arrow
a. is excluded from risk for HD.
b. is not excluded from risk for HD.
c. inherited an HD allele from his mother.
d. The boy’s risk cannot be determined from the information given.
Problems Section 12
1. Which of the hemoglobin designations below best describes the relationship of subunits in the
quaternary structure of adult hemoglobin?
a. (alpha1-alpha1)(beta1-beta1)
b. (alpha1-alpha2-alpha3-alpha4)
c. beta-beta-beta-beta

d. (beta1-beta2-beta3-alpha1)
e. (alpha1-beta1)-(alpha2-beta2)
2.Blood is drawn from a child with severe anemia and the hemoglobin protein is degraded for
peptide and amino acid analysis. Of the results below, which change in hemoglobin primary
structure is most likely to correlate with the clinical phenotype of anemia?
a. ile-leu-val to ile-ile-val
b. leu-glu-ile to leu-val-ile
c. gly-ile-gly to gly-val-gly
d. gly-asp-gly to gly-glu-gly
e. val-val-val to val-leu-val
3.An adolescent presents with shortness of breath during exercise and is found to be anemic. A
hemoglobin electrophoresis is performed that is depicted in the figure below. The adolescent’s
sample is run with controls including normal, sickle trait, and sickle cell anemia and serum. The
adolescent is determined to have an unknown hemoglobinopathy. Which one of the lanes contains the
adolescent’s sample?
a. lane A
b. lane B
c. lane C
d. lane D
e. lane E
4. Hemoglobin A
2
a. is a pathological hemoglobin.
b. is a fetal hemoglobin.
c. is a normal hemoglobin.
d. contains δ-globin chains rather than β-globin chains.
5.A particular β-globin allele occurs in northern European populations with an average frequency approximating
1/10,000. This allele is most likely maintained in these populations by
a. heterozygous advantage. c. assortative marriage.
b. mutation. d. migration.

6.Choose from the following: What is the most common mechanism of mutation giving rise to alpha
Thalassemias?
a. unequal cross-over between homologous pairs
b. equal cross-overs between homologous pairs
c. point mutations
d. insertional mutagenesis
7. In reference to #6, how would you have answered if the question was “What is the most common
mechanism of mutation giving rise to beta Thalassemias?
8.The locus control region is located 20 kb upstream of the beta genes and their promoters. It is responsible for
both high level expression as well as the developmental timing of expression of the beta genes. How might
you imagine this functions?
a. the LCR provides an open chromatin domain that gives transcription factors access to the regulatory
elements in the cluster.
b. It acts a super-enhancer for transcription
c. It is highly homologous to the introns of the immunoglobulin locus facilitating class switching
d. It packs tighly around histones
9.A woman has sickle cell trait and her mate is heterozygous for Hb C. What is the probability that there child
will have no normal hemoglobin?
Match the following for 10-19:
10. complex beta thalassemia 1. Detectable Hb A
11. B+thalassemia 2. Three
12. # of alpha globin genes missing in HbH 3. beta-Thalassemia
13. 2 different mutant alleles at a locus 4. alpha-Thalassemia
14. prenatal diagnosis of sickle cell disease 5. high-level beta chain expression
15. insoluble beta chains 6. alpha Thalassemia trait
16. # of alpha globin genes missing in 7. genetic compound
hydrops fetalis with Hb Bart
17. locus control region 8. delta/beta genes deleted
18. alpha-/alpha- genotype 9. Four
19. increased HbA2 10. restriction enzyme Mst II

Problems Section 13
Data for Questions 1–4: A young girl presented with mental deterioration, failure to thrive, poor motor
development, hepatosplenomegaly, and generalized aminoaciduria. The patient died two months after
hospitalization. The autopsy report mentioned dense-staining cellular inclusions in neuronal elements of the
cerebral cortex, basal ganglia, and cerebellum. Metachromatic granules were also observed in liver, spleen, and
kidney. Liver biopsy specimens obtained prior to the patient’s death lacked superzymase activity, and very low
levels of this enzyme were found in fresh brain, kidney, and spleen preparations taken at autopsy. Superzymase is
also expressed in leukocytes. Both the father and mother of this patient possessed leukocyte superzymase
activities that were about half normal. Both parents have normal clinical phenotypes. An older brother of the
patient died several years earlier from a disease that resembled that in the patient. The remainder of the family
history is negative for the disease.
1. What type of inheritance best explains the transmission of the disease in this family?
a. Autosomal dominant d. X-linked recessive
b. Autosomal recessive e. Multifactorial
c. X-linked dominant
2.How would you explain the patient’s clinical symptoms?
a. The symptoms are most likely caused by two genes: one responsible for the mental effects, and one
causing the physical problems.
b. The symptoms are the result of several genes, each causing one feature of the disease.
c. One gene encodes superzymase, and all of the effects are caused by a central block created by
deficiency of this enzyme.
d. Two recessive mutations are involved: one causing superzymase deficiency, and the other responsible
for loss of a transport substance that is a common carrier for all of the amino acids appearing in the
urine.
e. None of the above
3. How would you account for the tissue differences in superzymase activity?
a. Modifiers in each tissue affect the expression of the superzymase structural gene.
b. Inhibitors in the liver totally block superzymase expression in that tissue.
c. More than one isozyme of superzymase exists. Liver has only one isozyme, while other tissues
possess more superzymase isozymes. The mutation only affects the isozyme expressed in both liver

and other tissues.
d. More than one isozyme of superzymase exists. Liver contains at least two isozymes, while other
tissues have one. The mutation affects the enzyme shared by all tissues.
4. How would you explain the granules present in the cells of this patient?
a. They may be accumulations of the substrate of superzymase.
b. They could be aggregations of a byproduct produced by a salvage pathway that usually does not
operate at significant levels in normal cells.
c. The granules may contain the substrate of another enzyme that is inhibited by high quantities of the
substrate of superzymase.
d. They are viral particles that were coincidentally observed in these tissues.
5. Which of the following traits illustrates the concept of genetic predisposition for human disease?
a. Cystic fibrosis d. LDL-receptor deficiency
b. Phenylketonuria e. All of the preceding
c. AAT deficiency
6. A couple has a child who has been diagnosed with a medium chain acyl coenzyme A dehydrogenase deficiency
(MCAD), a condition that affects the body’s ability to metabolize medium chain fatty acids. This couple is now
expecting another child. Given what you know about the inheritance of metabolic disorders, what is the risk that this
child will have MCAD?
7. How may the blood and urine levels of a patient with a mutation affecting the intracellular metabolism of an
amino acid differ from those of a patient who has abnormal transport of that amino acid across his proximal
tubule membranes?
8. Consider the following pathway:
Predict the consequences of a block between C and D.
9. Tay-Sachs disease causes cherry red spots in the eye, ‘startle’responses in infancy, neurodegeneration and
death. Heterozygotes with an abnormal Tay-Sachs allele are termed carriers. What is the risk that the
grandmother of an affected child is a carrier?
Questions 10–13. Match the following diseases with their enzyme/protein deficiency.
10. Phenylketonuria a. Tyrosinase
11. Tay-Sachs disease b. CFTR
12. Familial Type IIa Hypercholesterolemia c. Hexosaminidase B

13. Cystic fibrosis d. Phenylalanine hydroxylase
e. Hexosaminidase A
f. LDL-receptor
14. A girl seems normal at birth but begins flinching at loud noises (enhanced startle response) at age 6
months. Opthalmologic examination reveals a central red area of the retina surrounded by white tissue
(cherry red spot). The child initially can sit up, but then regresses so that she can’t roll over or recognize
her parents. Her physician suspects a lipid storage disease (neurolipidosis). If the diagnosis is correct,
what is the risk that the next child of these parents will be affected with the same disease?
The cause of Tay-Sachs disease is best described by which of the following?
a. excess of lysosomal enzyme in blood due to defective uptake
b. deficiency of a lysosomal enzyme that digests proteoglycans
c. deficiency of a membrane receptor that takes up proteoglycans
d. deficiency of a mitochondrial enzyme that degrades glycogen
15. A woman who married her first cousin wants to know what the risk of having a child with cystic
fibrosis is because her grandmother, who is also her husband’s grandmother, died of cystic fibrosis.
16. Which of the following is most likely in an untreated child with PKU?
a. elevated tyrosine
b. increased skin pigmentation
c. decreased skin pigmentation
d. normal phenylalanine hydroxylase levels
e. elevated alanine
Problems Section 14
1. A mutation in the pro alpha 1 chain of collagen is in general more deleterious than
a mutation in the pro alpha 2 gene of collagen for which of the following reasons:
a. post-translational modifications only occur on pro alpha chain1
b. post-translational modifications only occur on pro alpha chain 2
c. collagen molecules are formed by 2 pro alpha 1 chains and 1 pro alpha 2 chain
d. pro alpha 1 is the only chain able to associate with elastin
2. Mutations in pro alpha 1 chain lead to what kind of ratio of normal to mutant collagen chains?
3. Which of the characteristics below apply to the amino acid glycine?

a. has a hydrogen for a side chain, thus, is small
b. large molecular diameter interfering with alpha helix formation
c. hydrophilic, basic and charged
d. hydrophobic
4. Amino acid hydroxylation requires the reducing agent ascorbic acid, which is also known as vitamin C. Scurvy,
results from a deficiency of vitamin C. Which of the following symptoms might you expect to see in individuals with
scurvy?
a. neural tube defects.
b. Mental retardation
c. Brittle bones with fractures and bleeding tendencies
d. Digestion problems
5. Why did you answer 4 the way you did?
6. Little People of America is a support group for individuals with short stature that conducts many workshops and social
activities. Two individuals with achondroplasia meet and decide to marry and have children. What is their risk of
having a child with dwarfism?
a. 100%
b. 75%
c. 67%
d. 25%
e. ~0%
7. The diagnosis of osteogenesis imperfecta is most accurately performed by which of the following?
a. PCR amplification and DNA sequencing of type I collagen gene segments to look for point
mutations
b. Gel electrophoresis of labeled type I collagen chains synthesized in fibroblasts
c. PCR amplification and ASO hybridization to detect particular alleles
d. Northern blot analysis to examine RNA levels and size
e. Purfication and trypsin digestion of type 1 collagen to examine the peptides by 2 D gel
electrophoresis
8. A patient with Marfan’s syndrome is evaluated at a clinic. He is noted to have a tall, thin body, loose joints
and arachnodactyly. Opthalmologic examinination reveals lens dislocation. Echocardiogram reveals

dilation of the aortic root. A family history reveals that the patient’s parents are normal but that this
paternal grandfather and great-grandfather died in their 40s with lens dislocation and dissecting aortic
aneurysms. A sister is found to have a similar body habitus, dilation of the aortic root and normal
lenses. The different findings in these family members with the same disease is best described as:
a. pleiotropy
b. founder effect
c. variable expressivity
d. incomplete penetrance
e. genetic heterogeneity
9. Marfan’s syndrome is caused by which of the following mechanisms?
a. mutation that prevents addition of carbohydrate residues to the fibrillin glycoprotein

b. mutation in a carbohydrate portion of fibrillin
c. mutation that disrupts a secondary structure of fibrillin and blocks its assembly into microfibrils
d. mutation in a lysosomal enzyme that degrades fibrillin
e. mutation in a membrane receptor that targets fibrillin to lysosomes
Problems Section 15
1.Bill is the only person in his family affected with Duchenne muscular dystrophy. He has one unaffected brother
Joe. DNA analysis shows that Bill has a deletion in the DMD gene. Joe received the same maternal X
chromosome but without the deletion. What happened to account for this?
a. Bill and Joe have different fathers
b. Bill arose from a new mutation on the X chromosome from his mother
c. The mother may be a mosaic and the mosaicism occurred in her germline
d. The father is a mosaic and the mosaicism occurred in his germline
2. A woman with a hemophiliac father is married to a man with Becker muscular dystrophy. Both traits are
inherited as X-linked recessives. Patients with this mild form of muscular dystrophy are fertile and are
usually not confined to a wheelchair until their forties. What types of children may they have?
Daughters Sons
a. 1/2 at risk for dystrophy; 1/2 normal 1/2 hemophiliac; 1/2 normal
b. all normal 1/2 hemophiliac; 1/2 normal

c. all normal 1/2 at risk for dystrophy; 1/2 normal
d. 1/2 hemophiliac; 1/2 at risk for dystrophy 1/2 hemophiliac; 1/2 normal
e. 1/2 at risk for dystrophy; 1/2 hemophiliac 1/2 hemophiliac; 1/2 normal
Question 3: True or False

3. A phenotypically normal woman and a protanopic (red-blind) man cannot have a colorblind son.
4. Anhydrotic ectodermal dysplasia (AED) is inherited as an X-linked recessive trait. A daughter of a normal
man and heterozygous woman has AED. What is the most probable cause for the appearance of AED in this
girl?
a. Deletion of her normal allele d. Homozygosity for the trait allele
b. X-inactivation of her normal allele e. Both b and c above
c. Heterozygosity for the trait allele
5. What type of inheritance is most likely responsible for
inheritance of the trait in the above pedigree?
a. X-linked dominant d.
Autosomal dominant
b. X-linked recessive e. Y-linkage
c. Autosomal recessive
6. Based upon what you know relevant to X-linkage and the properties of X-linked genes, what would you expect for the
phenotype of a woman heterozygous for an X-linked recessive trait with specific effects, such as G6PD deficiency?
a. She would be intermediate between normal and a homozygous affected woman or hemizygous
male.
b. She would be normal.
c. She would be affected.
d. Her phenotype would usually be normal, but occasional affected heterozygotes would be anticipated
when X-inactivation in different cells silenced most of their normal G6PD alleles.
e. None of the above
7. Duchenne muscular dystrophy has a high mutation rate but shows no ethnic variation in frequency. Using
your knowledge of the dystrophin gene and the genetics of this disorder, choose the best explanation for why
this disorder is equally frequent in all populations:

a. Intrachromosomal recombination occurs on the X chromosome to give rise to this deletion
b. The large size of the dystrophin gene makes it an easy target for mutation
c. There is heterozygote advantage to having a mutation in the dystrophin gene
d. Point mutations in tbe promoter can occur in all races
8. XGA is an X-linked trait with lack of Xg(a) antigen being recessive to its presence. G6PD is also
X-linked, and the presence of enzyme activity is dominant to its absence. Phenotypes of individual
erythrocytes can be scored by using a fluorescent antibody specific for Xg(a) and a stain for G6PD activity.
If a woman is heterozygous at both loci and G6PD but not XGA is subject to X-inactivation, what pattern
of erythrocytes would you expect to see after treating them with the two reagents?
9. Amelogenesis imperfecta (hereditary enamel hypoplasia) is inherited as an X-linked dominant trait. Males
have a very thin, smooth layer of enamel which appears homogeneous. Heterozygous females have
irregularly thick and thin enamel, often having the appearance of vertical grooves. How would you
explain this sex difference?
a. Random X-inactivation leads to sectors of mutant and normal cells.
b. Somatic mutation limited to the female
c. The trait is really dominant in males and recessive in females.
d. The groove pattern is environmentally determined.
Data for Questions 10–14: The Bruton form of hypogammaglobulinemia is inherited as an X-linked recessive.
Circulating antibodies in these patients are grossly deficient. A woman had two brothers die from the disease.
Both of her parents and her husband have normal levels of gamma-globulin and normal antibody function.
10. What is the probability that this woman is a heterozygote?
a. 1 c. 1/2
b. 2/3 d. 0
11. If her first child is an affected male, what is the chance that the next child will be affected?
a. 1/8 c. 1/2
b. 1/4 d. 1
12. If the first child is a normal male, would the risk for an affected child
a. Increase?
b. Decrease?
c. Remain unchanged?

13. Why did you select the above response?
a. Risks based upon single-factor inheritance never change.
b. The genotype of the mother is established.
c. The genotype of the mother is unknown.
d. Risk to a future child decreases with increasing numbers of normal events, as long as the mother's
genotype has not been established.
e. Both c and d above
14. Suppose this woman produced a normal daughter and two normal sons. What is the probability that the
woman is a carrier?
a. 1/7 c. 1/3
b. 1/5 d. 1/2
15. A Nigerian medical student studying in the U.S. develops hemolytic anemia after taking the oxidizing antimalarial
drug pamaquine. This severe reaction is most likely due to
a. glucose-6-phosphate dehydrogenase deficiency
b. concomitant scurvy
c. vitamin C deficiency
d. diabetes
e. sickle cell anemia
16. In most patients with gout as well as those with Lesch-nyhan syndrome, purines are overproduced and
overexcreted. Yet the hypoxanthine analog allopurinol, which effectively treats gout, has no effect on the
severe neurological symptoms of Lesch-Nyhan patients because it does not
a. decrease de novo purine synthesis
b. decrease de novo pyrimidine synthesis
c. diminish urate synthesis
d. increase phosphoribosylpyrophosphate levels
17. The most common intrachromosomal recombination event resulting in an inversion is the cause of which of
the following diseases:
a. Duchenne muscular dystrophy
b. Becker muscular dystrophy
c. Glucose 6 phosphate dehydrogenase deficiency

d. Hemophilia A
e. Hemophilia B
Problems Section 16
For 1-13, match the disorder with the description
1. RNA binding protein a. Friedreich’s ataxia
2. founder effect b. Fragile X syndrome
3. protein kinase c. myotonic dystrophy
4. mitochondrial protein d. Huntington’s disease
5. hyper-methylation inhibits RNApolymerase from transcribing the gene
6. coding-region polyglutamine expansion
7. anticipation
8. abnormally high levels of iron in their heart tissue
9. free radical damage
10. expansion occurs during male meiosis
11. expansion occurs during female meiosis
12. may be caused by depletion of an RNA binding protein
13. autosomal recessive
14. A woman presents to you because she is concerned about her unborn child. She tells you that she has a
brother who looks normal but is “ a little slow” and whose speech is difficult to understand. Although
he is an adult and works at a local grocery store shelving produce, he still lives with his parents. You
suspect that he may have fragile X syndrome so you test her DNA and find that she has a repeat size of
75. How do you counsel her?
a. Her children will all be normal because her repeat size is not greater than 200
b. She may have an increased risk of experiencing premature menopause
c. All of her children will have fragile X syndrome.
d. She is at increased risk of having fragile X sons and daughters, although affected daughters will
be more mildly affected.
15. The ship Hopewell arrived on a small island several hundred years ago carrying numerous pilgrims
with diabetes insipidus. The disease is now known to be caused by mutant allele A and all of the
island residents have 10x the frequency of this allele than do people living on the mainland. Which

of the following terms best describes this phenomenon?
a. selection for allele A
b. linkage disequilibrium with allele A
c. linkage to allele A
d. founder effect for allele A
e. assortative mating for allele A
Problems Section 17
Questions 1-15: For the following viral vectors, match the following characteristics:
1. infects all cell types a. retroviruses
2. only infects dividing cells b. adenoviruses
3. integrates into the host DNA c. adenoassociated viruses
4. describes the HIV virus d. Lentiviruses
5. Is capable of replication
6. Can hold 30-35 kb of insert
7. Can hold only small inserts (5-10 kb)
8. Has no known adverse effects in humans
9. Is nontoxic to cells
10. Can exist as an episome (not integrated into the host DNA)
11. Has potential for insertional mutagenesis
12. Potential for a strong immunological response
13. Only provides transient expression of a given gene
14. RNA virus
15. DNA virus
16. What are the advantages and disadvantages of introducing non-viral DNA?
17. List the possible ways gene therapy could be used to treat tumor cells:
18. How does expression of thymidine kinase in tumor cells mediate cell death in the presence of gancyclovir?
For problems 19-23. In the RNAi (interfering RNA) pathway, match the enzyme with the function:
19. Dicer a. performs nucleolytic degradation of the RNA
20. Guide RNA b. RNA that is degraded
21. Helicase c. RNA that is found in the RISC complex that associates

with the target RNA
22. RISC complex d. The enzyme that processes the introduced double-
stranded RNA into 21-23 mers
23. target RNA e. an enzyme with unwinding activity
24. Choose the correct sequence for therapeutic cloning:
a. isolate the nucleus from the adult somatic cell of interest, inject it into an enucleated ovum, induce cell division,
isolate the inner cell mass, induce differentiation into the tissue of interest
b. isolate the nucleus from the adult somatic cell of interest, inject it into an enucleated ovum, induce cell division,
inject the blastocyst into a pseudopregnant carrier female.
c. Isolate the nucleus from the ovum, inject it into an enucleated somatic cell of interest, induce the somatic cell to
differentiate into the tissue of interest.
d. Isolate ES cells from the germ line of aborted fetuses and induce them to differentiate into the tissue of interest.
25. Which of the above is the correct sequence for reproductive cloning?
26. Why can’t you just take the existing 60 or so ES cell lines, figure out how to induce tissue-specific differentiation and
then transplant into the waiting recipients?
Problems Section 18
1.A family comes to clinic with multiple affected members. As you are taking down the information, you produce the
following pedigree:
What do you conclude from this pedigree and why?
2. A 6 year old child is referred to you because of developmental delays and mental retardation, reduced speech and
seizures. You note that the child has a stiff, jerky gait. The parents note that eventhough the child does not speak
much, he laughs excessively. Your provisional diagnosis is which of the following:
a. Angelman syndrome
b. Prader Willi syndrome
c. Fragile X syndrome
d. Myotonic dystrophy
3. For the above child, you have access to a genetic clinic and have suspicians about the molecular defect. You order
SNP analysis of the parents and child focusing on the UBE gene or the regions around it. Which of the following
outcomes are a possibility:
a. In the patient there is a deletion of the UBE gene on the maternally inherited chromosome

b. In the patient there is a deletion of the UBE gene on the paternally inherited chromosome
c. The patient inherited both chromosome 15s from the father
d. The patient inherited both chromsome 15s from the mother
e. The patient inherited chromosomes 15 from each parent, however, the maternal chromsome 15 has a deleted
imprinting center
4. What is the name of the phenomenon that gives rise to answers (c) and (d) above?
5. Molecularly speaking, how is the phenomenon of imprinting maintained?
6. The genesis of Prader-Willi syndrome by inheritance of 2 normal chromosomes from a single parent is an example of
which of the following:
a. germinal mosaicisim
b. genomic imprinting
c. chromosome deletion
d. chromosome rearrangement
e. anticipation
7. A child with severe epilepsy, autistic behavior, and developmental delay has characteristics of a condition known as
Angelman’s syndrome. Because of the syndromic nature of the disorder and the developmental delay, a karyotype is
performed that shows a missing band on one chromosome 15. Which of the following best describes this abnormality?
a. interstitial deletion on chromosome 15
b. terminal deletion on chromosome 15
c. pericentric inversion on chromosome 15
d. paracentric inversion on chromosome 15
e. 15q-
8. Prader-Willi syndrome involves a voracious appetite, obsesity, short stature, hypogonadisim, and mental disability. At
least 50% of Prader-Willi patients have a small deletion on the proximal long arm of chromosome 15. In detecting
Prader-Willi deletion, which of the following techniques would be the most accurate?
a. standard karyotyping
b. northern blotting of mRNAs transcribed from the deleted region
c. restriction analysis to detect DNA fragments from the deleted region
d. rapid karyotyping of the bone marrow
e. fluorescent in situ hybridization (FISH) analysis of peripheral blood lymphocytes using fluorescent DNA probes

from the deleted region
9. A karyotype is performed on an obese child and is entirely normal. Because you suspect Prader-Willi syndrome,
Southern blotting is performed to determine the origin of the patient’s chromosome 15. In the figure below, probe
D15S8 defines the four restriction fragment length polymorphisms (RFLPs) present in the DNA from the mother (M),
child (C), and father (F). Based on the D15S8 locus, what is the origin of the child’s two number 15 chromosomes?
a. one from the mother and one from the father
b. both from the father
c. both from the mother
d. from neither parent
e. cannot tell because the locus is deleted in the child
10. Because the figure in question 478 demonstrates that the child is missing both paternal chromosome 15 alleles,
nonpaternity is a more plausible explanation than uniparental disomy. The hypothetical southern blot below illustrates
M C F
a DNA fingerprinting analysis to examine paternity, where maternal (M) , child (C), and paternal (F) DNA samples
have been digested, blotted and hybridized simultaneously to the probes D7Z5 and D20Z1. The distributions of the
restriction fragment alleles suggest:
a. The child is adopted
b. False maternity (baby switched in the nursery)
c. False paternity
d. Correct maternity and paternity
e. None of the above
11. Many family studies employing DNA have the potential to demonstrate nonpaternity. If the physician
ordering these analyses does not discuss this possibility with the couples involved, she or he is in violation
of which of the following:
a. patient confidentiality
b. patient rights
c. informed consent
d. standards of care
e. malpractice guidelines
Problems Section 19

1. The age of onset of a degenerative neurologic disease is 35 years old. epidemiologic study of affected
persons indicates that most cases occur in the spring, are isolated (no neighbors or relatives are affected)
and occur equally among men and women. However, subset of cases consists of two affected siblings in
a family. The best description of this disease is:
a. inherited
b. genetic
c. sporadic
d. congenital
e. familial
2. A couple in your care has had three pregnancies. The first died shortly after birth from complications of
anencephaly. The second pregnancy resulted in a child with spina bifida. This child has paralysis of the
legs but is otherwise OK. Their third infant is free of handicaps. How would you counsel this family?
3. Based upon what you have learned about the multifactorial nature of birth defects, which of the following
are likely to be true?
a. Uniform occurrence of abnormalities in fetuses exposed to a teratogenic drug
b. Occurrence of birth defects in some infants exposed to a teratogenic drug but not in others
c. Fetuses exhibiting signs of teratogen-induced defects will display variable expressivity of the
abnormalities involved