Medical Genetics Midterm exam Test B

SINGLE BEST ANSWER

Questions 1 and 2:
You are asked to see a family in which a genetic condition, polydactyly (too many digits) is present in
multiple members. You find out that the grandmother had it, as well as two of her daughters and one son.
That son is the father of your consultand. Your consultand is affected, but his sister is not. All affected
persons are otherwise healthy.
1. The most likely inheritance pattern for this problem in this family is:
A) Autosomal Recessive
B) Autosomal Dominant
C) X-linked Recessive
D) X-linked Dominant
E) Y-linked
2. The risk for the consultand to pass the condition on to his children is:
A) 50%
B) 25%
C) 100% for daughters and 0% for sons
D) 50% for daughters and 0% for sons
E) 100%
3. Osteogenesis imperfecta type I is the mildest form of osteogenesis imperfecta because most
of the mutations that cause osteogenesis imperfecta type 1:
A) disrupt the folding of the triple helical domain of type I collagen near the carboxylterminal domain of the protein
B) disrupt the cleavage of the amino-terminal domain of the protein
C) result in no protein being produced from one allele (null allele)
D) result in 3 out of 4 of the type I collagen molecules that are produced to be abnormal
E) prevent the secretion of the alpha-2 chain because of leader-sequence mutation
4. Mitochondria are organelles that originated as endosymbiotic prokaryotes. Like chloroplasts in plants,
mitochondria have their own genome that is separate from the nuclear genome of the cell. It is possible
for a human disease condition to arise as a result of a mutation in the mitochondrial genome.
Mitochondrial disease most typically involves the cytochrome oxidase enzymes. Phenotypically these
diseases are most likely to effect:
A) Skeletal muscle and central nervous system
B) Cardiac muscle and liver
C) Central nervous system and blood
D) Gonads and liver
E) Cardiac muscle and blood
5. During the cell cycle, meaningful clinical cytogenetic data are most readily attainable in:
A) G1 phase
B) G2 phase
C) M phase
D) S phase
E) Go phase

6. The coefficient of inbreeding (F) for a half-sib mating is

A) 1/4
B) 1/8
C) 1/16
D) 1/32
E) 1/64
7. Determining if there is familial aggregation of a particular disease is useful for assessing whether
genetic factors play a role in causing the disease. Family aggregation studies can also determine:
A) the gene causing the disorder
B) the empiric risk that an unaffected family member will develop the disease
C) the environmental factors causing the disorder
D) how much a disease predisposition is environmental and how much is genetic
E) the Mendelian inheritance pattern
8. The measure of penetrance of a dominant disease can be thought of mathematically. Complete this
equation:
% penetrance =
A) p2 + 2pq + q2
B) expected phenotype distribution/observed phenotype distribution
C) # of people with the phenotype/# of people with the genotype
D) MM x MN
E) phenotype in one patient/ complete phenotype
9. A child is born and is found to have microcephaly (a small head) and a number of other features that
are unusual. You find out that his 36 year old mother was diagnosed as a child with phenylketonuria
(PKU), and was on a restricted diet until she was 25 years old. Though you have some test pending, you
make a diagnosis of PKU embryopathy. The manifestations are worse than those of the PKU in the
mother because:
A) the mother is henuzygous for this X-linked disease and has fortunate Lyonization
B) the mother has fewer mutated mitochondria
C) the triplet repeat mutation expanded and caused molecular and clinical anticipation
D) the baby's disease is complicated by a chromosomal aneuploidy
E) elevated phenylalanine levels in the fetus are teratogenic
10. The purpose of a genetic linkage study is to:
A) Discover the pleiotropic effects of a gene
B) Examine the DNA sequence of a mutational site
C) Determine the map location of a disease gene
C D) Determine if coatings are consanguineous
E) Compare concordance in MZ and DZ twins
11. A couple's second child is 3 years old and has just been diagnosed with Tay-Sachs Disease
The chance that the 9-year-old full sibling is a carrier of the disorder is:
A) 1/2
B) 1/4
C) 2/3
D) 1/2 x 1/2
E) Dependent on the sex of the proband

12. The most significant difference between mitosis and meiosis is:
A) in meiosis there are 2 cell divisions without an intervening S phase
B) only meiosis takes place in the gonads
C) in mitosis, the chromosome number is reduced from 2n to n
D) meiosis freezes in stage 1 in both genders
E) mitosis occurs in all cells for the entire life span of a person
13. Mutations of autosomal genes produce disorders that may show either a dominant or recessive
inheritance pattern. A dominant pattern is typically exhibited when the normal gene product:
A) Has enzyme activity
B) Functions primarily in early embryonic development
C) Has a limited tissue distribution
D) Functions as a structural protein
E) Is an enzyme cofactor
14. The first gene found solely by positional cloning without the use of cytogenetic clues was:
A) Huntington Disease
B) Retinoblastoma
C) Hemophilia A
D) Cystic Fibrosis
E) Polycystic Kidney Disease
15. A recently married couple requests counseling because they have just learned that they are first
cousins. They are at an increased risk to have children affected with:
A) Multifactorial disorders
B) Autosomal dominant disorders
C) Mitochondrial disorders
D) Chromosomal disorders
E) Sex-Linked disorders
Questions 16 and 17
A protein is a homodimer, the subunits of which are coded for by an autosomal gene. A
nonsense mutation in the third exon of this gene results in premature termination of the
gene product.
16. If an individual is, heterozygous for this nonsense mutation their biochemical phenotype would show:
A) complete lack of enzyme activity
B) 50% of normal activity
C) normal enzyme activity (100%) because of compensation by the normal gene copy
D) greater than 100% of normal activity because of compensation by the normal gene copy
E) a variable level of activity dependent upon the Lyonization of the chromosomes
17. The inheritance pattern for a disease phenotype (0% of normal activity) of the above described protein
would most likely be:
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial (maternal)
D) X-linked dominant
E) X-linked recessive

18. In a molecular diagnostic study using linkage, a result is said to be informative if:
A) the disease gene in question has been sequenced (cloned)
B) detailed phenotypic information is available from the primary relatives
C) all of the proband's primary and secondary relatives are available for study
D) it reveals non-paternity
E) the disease and non-disease haplotypes are distinct
19. In meiosis (assuming that no crossing over has occurred) homologous chromosomes segregate at:
A) The first but not the second meiotic division
B) The second but not the first meiotic division
C) Both the first and second meiotic divisions
D) Neither the first nor the second meiotic division
E) Homologous chromosomes segregate in mitosis, not meiosis
20. It is well documented that chromosomal aneuploidies increase with the increasing maternal age.
Which type of genetic condition increases in frequency with increasing paternal age?
A) Uniparental Disomy
B) New Autosomal Dominant Disease
C) Mitochondrial Disease
D) Y-Linked Diseases
E) Somatic Mosaicism
21. To date, there are 11 diseases known to be caused by a recently discovered type of mutation referred
to as an expanding triplet repeat mutation. These diseases all seem to involve the neuromuscular systems
and many are degenerative diseases. Presumably, the expansion of the triplet repeat mutation disrupts the
normal transcription/translation of the gene. Relative to the genes themselves on a molecular level, the
triplet repeats are found:
A) in the coding regions of the genes
B) at different sites depending upon the gene
C) in the non-coding regions of the genes
D) only on the maternal chromosome
E) in the transcribed mRNA
22. In the last century, a group of French Canadians moved to southern Louisiana. One of the members of
that community was a gentleman who had an Ashkenazic Jewish heritage, but had recently convened to
Catholicism and had joined the group, the Acadians, in their move. He was a carrier for Tay-Sachs
disease. He fathered many children and now Tay- Sachs disease had an increased frequency among the
Acaidian population in Louisiana. This phenomenon is referred to as:
A) Consanguinity
B) Genetic Drift
C) Complementation
D) Allelism
E) Founder Effect
23. Mendel's Law of Independent Assortment states that:
A) blending of characteristics of the parents does not occur
B) two members of a single gene pair are never found in the same gamete
C) how one gene pair segregates is unrelated to how another gene pair segregates
D) members of a given species preferentially mate with similar partners
E) the presence of the phenotype is independent of the presence of the genotype

24. A gene is found that is maternally imprinted. A child is born and found to have a deletion of the
paternal copy of that gene. Phenotypically that child is:
A) normal because he has one functional copy of the gene
B) abnormal because he is a male
C) abnormal because he does not have a functional copy of the gene
D) normal because the `turned-off gene is the deleted one
E) abnormal because he is missing contiguous genes
25. The term `dominant negative allele' refers to a situation in which:
A) A mutation leads to the production of no protein from one allele
B) the product of the abnormal allele disrupts the function of the product of the normal allele
C) a missense mutation results in the production of an unstable protein that is degraded within the
cell
D) a retrotransposable element is inserted into a dominant disease gene
E) a mutation in the promotor for a gene results in reduced transcription of the gene and therefore
decreased protein product
26. Pedigrees are a valuable tool for understanding the inheritance pattern of a disease within a
family. At times, it can be difficult to decipher the pattern because of ascertainment
problems and the variation in severity of the disease among family members. The most
significant clue that a pedigree represents an autosomal dominant inheritance pattern rather
than an X-linked pattern is that:
A) there will be a clearly affected person in each generation
B) there are equal numbers of affected males and females
C) all males live long enough to be able to father children
D) there is male-to-male transmission evident at least once
E) the females are more severely affected than the males
27. At this point in time, scientists have identified many of the genes responsible for common
genetic diseases. When possible, diagnostic studies of such a disease in a family can be
accomplished by direct mutation analysis. Occasionally, linkage analysis is useful as a
diagnostic tool. Linkage analysis is most frequently useful when:
A) there is more than one possible disease mutation in a gene
B) not all family members are available for study
C) the carrier or affected status of other family members is unclear
D) the precise locus of the gene is not known
E) there is more than one gene known to be involved in the disease phenotype
28. A woman knows that she is a carrier for cystic fibrosis, an autosomal recessive disease.
Her husband's carrier status has never been tested. If incidence of the disease in the
general population is 1 in 1600 live births, what is their baseline risk for having a child
with cystic fibrosis?
A) 1/4
B)1/20
C) 1/40
D) 1/80
E) 1/200
29. The type of study most useful for determining how much of a disease susceptibility is genetic and
how much is environmental is a
A) linkage study.
B) association study
C) twin study
D) segregation analysis
E) prevalence analysis

30. Which of the common chromosomal aneuploidies does not correlate with advancing maternal age?
A) Down syndrome (trisomy 21)
B) Turner syndrome (45,X)
C) Edwards syndrome (trisomy 18)
D) Patau syndrome (trisomy 13)
E) Klinefelter syndrome (47,XXY)
31. A couple comes to see you because they are related and have heard that they are at an
increased risk of having a child with a genetic condition. Both of them are of Ashkenazic
Jewish descent. They tell you that the man's brother has cystic fibrosis, and that several of
their mutual relatives have spina bifida. Additional information that you need before giving
them any information includes:
A) the degree of relationship between the couple
B) whether the couple is related through the maternal or paternal sides
C) the severity of the cystic fibrosis in the man's brother
D) whether the couple is willing to use sperm donation
E) the reason that they intermarried
32. If a patient is found to have a chromosomal translocation involving homologous chromosomes,
then the risk of having a chromosomally unbalanced offspring is:
B) 25%
C) 50%
D) 100%
E) dependent upon the age of the mother
Questions 33 and 34
Apolipoprotein E has received much attention recently because of associations with both
cardiovascular disease and Alzheimer's disease. There are 3 common alleles; namely, E2, E3
and E4. Consider the following genotypes and counts:
Genotype

Number

E2E2
E2E3
E2E4
E3E3
E3E4
E4E4

2
64
7
711
169
11

Total

964

33. What is the frequency of the E2 allele?

A).002
B) .039
C) .076
D) .175
E) .738

34. What is the frequency of the E3 allele?

A) .858
B) .738
C) .979
D) .711
E) .500
Questions 35 and 36
Suppose that in another sample of data, one obtained frequencies of E2, E3 and E4 as follows:
f(E2) =.10
f(E3) =.70
f(E4) =.20
35. In a sample of 1000 individuals, how many E3E4 heterozygotes would you expect?
A) 700
B) 280
C) 140
D) 70
E) 20
36. Linkage analysis requires that at least one parent be heterozygous at the marker locus. Using
the frequencies in problem 34, how many of 1000 individuals are expected to be heterozygous?
A) 140
B) 700
C) 460
D) 280
E) 28
37. In normal, dividing human lymphocytes and fibroblasts, the duration of one cell cycle is on the order
of:
A) 1 to 2 hours.
B) 5 to 6 hours.
C) 20 to 24 hours.
D) 48 to 72 hours.
E) 72 to 96 hours
38. An example of a pure environmental disease (without any genetic component) is:
A) Bee sting allergy
B) AIDS
C) Asbestosis
D) Electric shock
E) Alcoholism
39. BRCA 1 and BRCA2 are the two recently described tumor suppressor genes that are found to
predispose to breast cancer. Together they account for about what percentage of breast cancer?
A) 5% in women and 50% in men
B) 5%
C) 50%
D) Depends upon the age of the person in question
E) 85%

Questions 40 and 41:

Three years ago, a boy with isolated cleft lip was born to a couple. They were counseled at the
time that this was a multifactorial trait and carried an empiric recurrence risk of approximately
3%. The mother recently gave birth to another boy with isolated cleft lip and they seek further
counseling.
40. Their recurrence risk for future pregnancies is:
A) Increased approximately double
B) Unchanged
C) Reduced to nearly zero since they have now had their affected child
D) Increased dramatically to 50% since both affected infants were boys
E) Unable to be determined
41. What is the chance that the affected boys will transmit the isolated cleft lip to their children?
A) The same as for the general population
B) Increased because they are affected and have a positive family history
C) Unable to be determined
D) Depends on the age when the affected boys have children
E) Less than the general population
42. Hardy-Weinberg equilibrium is observed under certain conditions. One population phenomenon that
is required in order for Hardy-Weinberg to be effective is:
A) selection
B) small population size
C) decreased fitness
D) random mating
E) migration
Questions 43-47
Mary is a 27 year old woman who is very involved in the mucopolysaccharidosis (MPS) support group.
Mary's sister, Jane, died of Hurler syndrome (alpha-L-iduronidase deficiency) at age 8 years. Mary met
two very nice men at the support group meeting, Joe and Bob, both of whom are affected with an MPS.
Joe has Scheie syndrome (alpha-L- iduronidase deficiency) and Bob has Hunter syndrome (iduronate
sulfatase deficiency) mild form. All of the defects are verified by enzyme testing. Mary has been dating
Joe and Bob.
43. If Mary marries Joe, based on the information presented above, what is the chance that they would
have a child affected with an MPS?
A) Negligible
B) 1/8
C) 1/4
D) 1/3
E) 1/2
44. If Mary and Joe do have a son affected with an MPS, the child's genotype and clinical findings would
most likely be an example of which genetic principle(s)?
A) Locus heterogeneity
B) Clinical heterogeneity
C) Allelic heterogeneity
D) Locus and clinical heterogeneity
E) Clinical and allelic heterogeneity

45. Mary and Joe's child who is affected with an MPS would also illustrate which of these genetic
principles?
A) Founder effect
B) Homozygote for alpha-L-iduronidase mutation
C) Compound heterozygote for alpha-L-iduronidase mutation
D) Hemizygous for alpha-L-iduronidase mutation
E) Genetic heterogeneity
46. If Mary marries Bob, what is the chance that they would have a child affected with an
A) Negligible
B) 1/8
C) 1 /4
D) 1/3
E) 1/2
47. Hurler syndrome (alpha-L-iduronidase deficiency) which affected Mary's sister, and Hunter syndrome
(iduronate sulfatase deficiency) in the severe form can have clinically indistinguishable phenotypes. This
is an example of which genetic principle(s)?
A) Locus heterogeneity
B) Clinical heterogeneity
C) Allelic heterogeneity
D) Locus and clinical heterogeneity
E) Clinical and allelic heterogeneity
MULTIPLE MATCHING
For each item, select the one lettered option that is most closely associated with it. Each lettered option
may be selected once, more than once, or not at all.
A) Missense mutation
B) Nonsense mutation
C) Frameshift deletion
D) Large deletion
E) Large duplication
F) RNA splicing mutation
Match the description below with the type of mutation that it represents
48. A patient has Duchenne Muscular Dystrophy (DMD) because exons 38-44 and the intervening
intronic DNA are missing.
49. Tay-Sachs disease (hexosaminidase A deficiency) in 18% of Ashkenazi Jews and <1% of nonAshkenazi is due to a G->C at exon 12 resulting in inclusion of intron 12 in the mRNA.
50. A patient has Duchenne Muscular Dystrophy (DMD) because he has two copies of exons 41-45.
51. Most patients in the United States have cystic fibrosis (CF) because of the deletion of 3 base pairs
resulting in the loss of a phenylalanine at codon #508.
52. A patient with neurofibromatosis type I (NF1) has a change in the first base pair of a glutamine (CAG)
to create a STOP (UAG) codon in exon 2. There is no protein produced because of this change.

53. An individual has mild PKU because one copy of the phenylalanine hydroxylase gene has a change at
codon #158 of an arginine to a glutamine and the other copy of the phenylalanine hydroxylase gene has a
change at codon #261 of arginine to glutamine.
For each item, select the one lettered option that is most closely associated with it. Each lettered option
may be selected once, more than once, or not at all.
A) Imprinting
B) Mitochondrial Inheritance
C) Multifactorial Inheritance
D) Sex - Limited
E) Hemizygous
F) Haplotype
G) Mendelian Inheritance
H) Autosomal Recessive Inheritance
I) Autosomal Dominant Inheritance
J) Sex - Linked
K) X-Linked Recessive
L) X- Linked Dominant
M) Y-Linked
N) Uniparental disomy
Match the term listed above with its definition:
54. Classic forms of single-gene inheritance
55. Inheritance pattern of a gene on an X or Y chromosome
56. Inactivation of a gene or genes dependent upon the gender of the transmitting parent
57. Inheritance of extra-nuclear genetic material
58. Parents of an affected child are obligate carriers of the disease gene
59. Having only one allele at a locus
60. A specific combination of linked alleles
For each item, select the one lettered option that is most closely associated with it. Each lettered option
may be selected once, more than once, or not at all.
A) Allelic heterogeneity
B) Clinical heterogeneity
C) Locus heterogeneity
D) Genetic drift
E) Founder effect
F) Compound heterozygote
Match the term above with it's best definition:
61. The production of clinically different phenotypes from mutations in the same gene.
62. The situation in which mutations at two or more distinct loci can produce the same or closely
similar phenotypes.
63. The situation in which there are different mutant alleles at the same locus, each capable of

producing an abnormal phenotype.

64. The random fluctuations of gene frequencies in populations .
65. An individual with two different mutant alleles at the same locus
66. A high frequency of a mutant gene in a population founded by a small ancestral group when
one or more of the founders was a carrier of the mutant allele. Ij
A) White
B) Black
C) Hispanic
D) Asian
E) Middle Eastern
F) Mediterranean
G) Ashkenazic
Match the genetic disease with the ethnic group in which it is considered to be most common.
67. Alpha thalassernia
68. Beta-Thalassemia
69. Gaucher Disease
70. Phenylketonuria
For each item, select the one lettered option that is most closely associated with it. Each lettered option
may be selected once, more than once, or not at all.
A) Autosomal Dominant inheritance
B) Autosomal Recessive inheritance
C) X-linked Dominant inheritance
D) X-linked Recessive inheritance
E) New atosomal dominant mutation
F) New X-linked mutation
G) Chromosomal aneuploidy
H) Chromosomal rearrangement
Match each clinical situation with the most likely etiology.
71. Two maternal uncles with a clinical picture similar to the affected male child
72. Advanced paternal age
73. Advanced maternal age
74. Recurrent early pregnancy losses
75. Consanguinity

ANSWERS:
1.
2.
3.
4.
5.
6.
7.
8.
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10.
11.
12.
13.
14.
15.
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23.
24.
25.
26.
27.
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30.
31.
32.
33.
34.
35.
36.
37.
38.

B
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D

39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
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60.
61.
62.
63.
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65.
66.
67.
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70.
71.
72.
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74.
75.

B
A
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F
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C
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J
A
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F
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C
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B