Boards Style Questions

Question 1

Assume that 500,000 serial newborns were examined for new mutation cases of a dominant disorder with 100% penetrance. Ten affected infants were found with unaffected parents. Which of the following represents the calculated mutation rate?

A. 1 x 10-6
B. 2 x 10-6
C. 1 x 10-5
D. 2 x 10-5
E. 4 x 10-5

Answer 1

For the direct method of estimating the mutation rate:

Number of sporadic cases with condition
µ = 2 x numbers of individuals examined x #sporadic cases

The correct answer is C

Question 2

A couple are both carriers for an autosomal recessive disorder. They have four children. What is the probability that at least one child is affected?

A. 40/256
B. 81/256
C. 160/256
D. 175/256
E. 216/256

Answer 2

The easiest approach is to calculate the probability that none of the children is affected which is
(3/4)^4

This is 81/256. The difference (175/256) is the probability that at least one child will be
affected. It is not as easy to calculate the probability, for example, that two children would be affected and two children would be unaffected. This would involve using the binomial expansion or making very careful calculations to consider all the possible birth orders and multiplying these
out.

The correct answer is D.

Question 3

What is the coefficient of inbreeding (F) for a mating of half-siblings?

A. 1/4
B. 1/8
C. 1/16
D. 1/32
E. 1/64

Answer 3

The correct answer is B.

Question 4

A couple requests genetic testing for their newborn child (arrow) who is at risk of a sex-linked recessive disorder that affects the child’s brother and uncle. A linkage study is performed using a marker closely linked to the disease locus. There are two alleles at the marker site: A and B, and the distance between the marker locus and the disease locus is estimated to be 5 cM. What is the
risk of this child developing signs of the disorder, assuming complete penetrance?

A. 0.0475
B. 0.0500
C. 0.0950
D. 0.0975
E. 0.1000

Pedigree: (3 generations)

Couple (A & AB) have 2 sons A (affected) & B. AB has a brother who was affected and passed.

Answer 4

Based on the affected sibling, the mother most likely has the A allele in coupling with the
disorder. The risk to the child is therefore 2θ – 2θ^2= 0.0950.

The correct answer is C.

Question 5

I-1 was affected with Hemophilia (Factor VIII deficiency). What is the probability that the
pregnancy (IV-4) will result in a boy affected with Hemophilia?

A. 1/4
B. 1/8
C. 1/9
D. 1/18
E. 1/36

Pedigree: (4 generations)

I Couple: Male 1 (affected & deceased) and female 2

II Daughter of couple (1) and a man who married into the family (2)

III Daughter of couple from II (I) and a man who married into the family (2)

IV Three sons from III couple and a current pregnancy

Answer 5

Bayes it out –> The correct answer is E.

Question 6

A couple presents for prenatal counseling and you obtain the family history documented in the pedigree below. They have two healthy sons and she is pregnant again. What is the approximate probability that her fetus will be severely affected with hydrocephalus?

A. 1/5.
B. 1/8.
C. 1/10.
D. 1/20.
E. 1/32.

Pedigree: (4 generations)

I Female (carrier) & Male (unaffected) (Couple)
II Daughter (Carrier), son (affected & deceased) (children of the daughter from couple I)
III Son (affected), daughter (unaffected), daughter (unaffected) (children of the daughter from couple II)
IV 2 unaffected sons and 1 pregnancy (children of the first daughter from couple III)

Answer 6

Bayes it out –> The correct answer is D.

Question 7

Assume a three allele autosomal DNA polymorphism with gene frequencies of 0.50, 0.25, and 0.25. What proportion of the population will be heterozygous for these polymorphisms?

A. 4/16 (0.25)
B. 6/16 (0.375)
C. 8/16 (0.5)
D. 10/16 (0.625)
E. 12/16 (0.75)

Answer 7

The correct answer is D.

Question 8

A woman has a child with an autosomal recessive disorder that affects 1:40,000 in the population. She remarries and the couple requests recurrence risk counseling. What is their approximate risk
of having an affected child?

A. 1/500
B. 1/400
C. 1/200
D. 1/100
E. 1/50

Answer 8

The correct answer is B.

Question 9

What is the probability that a couple who are both heterozygous for the (F508 mutation for CF will have two affected and two unaffected with CF if they have four children?

A. 9/32
B. 9/64
C. 9/128
D. 27/128
E. 27/256

Answer 9

The correct answer is D.

Question 10

Assume you discover a new X-linked platelet antigen detected by a monoclonal antibody.
Heterozygous and homozygous positive females are antigen positive. You find 20% of males to be antigen positive and 80% to be antigen negative. Assuming Hardy-Weinberg equilibrium, what percent of females would you predict to be antigen positive?

A. 16%
B. 20%
C. 32%
D. 36%
E. 40%

Answer 10

The correct answer is D.

Question 11

Assume the following frequencies for the ABO blood group. The A allele = 0.30; the B allele = 0.10; and the O allele = 0.60. What percent of people should be blood group A?

A. 9%
B. 18%
C. 27%
D. 36%
E. 45%

Answer 11

The correct answer is E.

Question 12

A recessive condition has a population frequency of 1:90,000. Choose the number below that is closest to the number of generations required to reduce the allele frequency by half, assuming that
all homozygous individuals are unable to reproduce?

A. 50
B. 75
C. 150
D. 300
E. 600

Answer 12

The correct answer is D.

Question 13

There is a three allele DNA polymorphism. A 10 kb fragment has an allele frequency of 0.10; a 7 kb fragment has an allele frequency of 0.10; and a 5 kb fragment has an allele frequency of 0.80. Assuming Hardy-Weinberg equilibrium, what percent of individuals should be
heterozygous for this polymorphism?

A. 34%
B. 36%
C. 50%
D. 64%
E. 66%

Answer 13

The correct answer is A.

Question 14

A GT repeat polymorphism has five alleles all with a frequency of 0.20. What proportion of
people should be heterozygous (informative)?

A. 0.10
B. 0.20
C. 0.50
D. 0.80
E. 0.90

Answer 14

The correct answer is D.

Question 15

You find an autosomal (two allele) RFLP and 25% of people are homozygotes for the upper band. What should be the allele frequency for that band?

A. 0.05
B. 0.10
C. 0.125
D. 0.25
E. 0.50

Answer 15

The correct answer is E.

Question 16

A couple seeks counseling regarding their risk of having a child with an autosomal recessive condition that affects the brother of one partner (see pedigree). The population frequency of the
disorder is 1:400. What is the risk to one of their offspring of being affected?

A. 1/40
B. 1/60
C. 1/80
D. 1/100
E. 1/120

Pedigree:

Couple (Male and Female), the male has one affected brother

Answer 16

The correct answer is B.

Question 17

What is the coefficient of inbreeding (F; equal to the chance of homozygosity by descent) for the child of the mating shown below?

A. 1/4
B. 1/8
C. 1/16
D. 1/32
E. 1/64

Pedigree: 5 generations

I Male and female couple

II Two males (Children of I)

III Each son has a daughter

IV One daughter has a son [*** This son is married to the other female right across]

V 1 pregnancy (of the couple IV)

Answer 17

The correct answer is D.

Question 18

A couple comes to you for genetic counseling. The wife had two siblings that died from Werdnig-
Hoffman syndrome (or spinal muscular atrophy 1, SMA1), an autosomal recessive disease with a
prevalence of approximately 1 in 20,000 livebirths. The husband reports a negative family history. What is the probability that this couple will have a child with SMA1?

A. 1 in 70
B. 1 in 120
C. 1 in 240
D. 1 in 360
E. 1 in 440

Answer 18

The correct answer is E.

Question 19

A 35-year old man presents for genetic counseling because his mother recently died from an autosomal dominant late-onset progressive neuromuscular disorder. By age 35 years, 75% of individuals carrying the mutant gene have begun to show symptoms of muscle weakness and
slurred speech. A thorough evaluation by a neurologist did not detect any signs of this condition. The gene for this condition is unknown and there are no available carrier tests. What is the likelihood that this man inherited the mutant gene from his mother?

A. 1 in 5
B. 1 in 10
C. 1 in 20
D. 1 in 30
E. 1 in 50

Answer 19

Bayes it out –> The correct answer is A.

Question 20

Which of the following numbers below is the closest estimate of the mutation rate for an
autosomal dominant disorder with a population frequency of 1:5,000 in which reproductive fitness is approximately 0.3?

A. 0.0001
B. 0.0002
C. 0.0003
D. 0.0004
E. 0.0005

Answer 20

The correct answer is A.

Question 21

Linkage is a violation of which of the following genetic concepts?

A. Hardy-Weinberg equilibrium
B. Mendel’s law of independent assortment
C. Mendel’s law of segregation
D. Recombination
E. Variability of expression

Answer 21

The correct answer is B.

Question 22

Which of the following families are completely informative for linkage analysis?

A. a and b
B. a and d
C. b and c
D. b and d
E. c and d

Answer 22

The correct answer is E.

Question 23

The presence of an allele or genotype at one locus being necessary for the expression of a
genotype at a second locus is described by which of the following genetic concepts?

A. pleiotropy
B. penetrance
C. linkage disequilibrium
D. variable expression
E. epistasis

Answer 23

The correct answer is E.

Question 24

A couple has a son with a multifactorial disorder in which it is more common for females to be affected. Which of the following statements about recurrence risk is true?

A. Recurrence is higher for a next child than if a daughter had been affected, and would be higher
for a daughter than a son
B. Recurrence is higher for a next child than if a daughter had been affected, and would be higher
for a son than a daughter
C. Recurrence is lower for a next child than if a daughter had been affected, and would be higher
for a daughter than a son
D. Recurrence is lower for a next child than if a daughter had been affected, and would be higher
for a son than a daughter
E. Recurrence is 50% since a son is affected.

Answer 24

This is an example of the Carter effect. Since the disorder is more common in daughters, the fact that a son was affected says that the liability in the couple must be higher than if a daughter had been affected. This makes the recurrence risk higher for the next child, but recurrence for this trait is always higher for a
daughter.

The correct answer is A.

Question 25

Mutations in the CFTR gene can affect multiple organ systems, including respiratory, gastrointestinal, and reproductive systems. This is an example of which of the following genetic concepts?

A. pleiotropy
B. penetrance
C. linkage disequilibrium
D. variable expression
E. epistasis

Answer 25

The correct answer is A.

Question 26

Males with two mutations in the CFTR gene can have classic CF (lung involvement, pancreatic insufficiency, male infertility) or only infertility. This is an example of which of the following genetic concepts?

A. pleiotropy
B. penetrance
C. linkage disequilibrium
D. variable expression
E. epistasis

Answer 26

The correct answer is D.

Question 27

A GeneReviews article notes the incidence of an autosomal recessive disease is 1 in 10,000. A man has an affected child and has remarried and his new wife is pregnant. His mutation is known and is found to be transmitted to the fetus. Carrier detection for the new wife is impractical. What is the chance the fetus is affected?

A. 1 in 25
B. 1 in 50
C. 1 in 64
D. 1 in 100
E. 1 in 200

Answer 27

The correct answer is D.

Question 28

A woman has a son with an X-linked recessive lethal disorder and no other family history of the condition. Her daughter has one healthy son. What is the daughter’s risk of being a carrier?

A. 0.10
B. 0.20
C. 0.33
D. 0.50
E. 0.66

Answer 28

Bayes it out –> The correct answer is B.

Question 29

A couple’s first child is a boy with a very severe X-linked disease. There is no carrier testing for this disease and the incidence is 1 in 100,000 boys. Neither partner has a family history of this disease. The probability that the couple will have another affected child is about

A. 1/2
B. 1/3
C. 1/4
D. 1/6
E. 1/12

Answer 29

The correct answer is D.

Question 30

What is the approximate odds ratio of a disorder in a person who carries an allele that is seen in 30% of those with the disorder but only 20% of controls?

A. 1.5
B. 0.8
C. 1.7
D. 1.9
E. 2.4

Answer 30

The correct answer is C.

Question 31

Consider the pedigree shown below, where an autosomal dominant disorder is being transmitted. A four allele marker has been genotyped and the corresponding alleles for are shown below the symbol for each individual.

What is the recombination frequency for the marker and disease locus?
A. 0
B. 1/8
C. 3/8
D. 1/2
E. 5/8

Answer 31

The correct answer is B.

Question 32

Leevi, a 32-year-old man of Finnish descent had a sibling who died at the age of 10 from cystic fibrosis (CF). Leevi, who does not himself have CF, has recently married and would like to start a
family, but is concerned about the risk of passing CF to his children. DNA samples are not available from his brother or from his parents, who are both deceased. He undergoes DNA testing
for the 70 most common CFTR mutations – a panel that detects 90% of the mutations found among individuals of northern European descent. He tests negative for all 70 mutations. Given
this information, what is the probability that he is a heterozygous carrier for CF?

A. 2/3
B. 1/4
C. 1/6
D. 1/15
E. 1/25

Answer 32

The correct answer is C.

Question 32

Elizabeth’s maternal grandfather has hemophilia due to a factor VIII deficiency. Elizabeth has married an unaffected man and has four healthy sons. Elizabeth is pregnant again with a male fetus. What is the approximate probability that this fetus will develop hemophilia?

A. 0
B. 1/4
C. 1/25
D. 1/33
E. 1/50

Answer 32

Bayes it out –> The correct answer is D.

Question 33

Rob’s father has Huntington’s disease. Rob’s mother has no family history of Huntington’s
disease. Although Rob does not want to know if he has inherited the mutation, he is concerned about the potential risks for his children. Rob’s wife, who has no family history of Huntington’s disease, is pregnant. Prenatal testing is performed, using the alleles of an STR marker linked (q = 0.0) to the Huntington gene. The allele results are shown below on the pedigree of Rob’s family.

Using this information, what is the approximate chance that the fetus has inherited the mutated
(expanded) copy of the Huntington gene?

A. 0
B. 1/4
C. 1/2
D. 3/4
E. 1

Answer 33

The correct answer is A.

Question 34

A 22-year-old man is at 50% risk of having inherited a mutation for a dominantly inherited disorder. He has no signs of the disorder, but the condition displays age-dependent penetrance, so that 20% of individuals at age 22 would expect to be affected. What is his approximate risk of
having inherited the mutation?

A. 0.86
B. 0.52
C. 0.44
D. 0.24
E. 0.20

Answer 34

The correct answer is C.

Question 35

Mr. and Mrs. Smith come to see you in your clinic very distressed. At 38 years old, Mrs. Smith is pregnant with her fifth child. Her firstborn died from complications of cystic fibrosis. The couple’s three other children are not affected with this condition, but Mr. and Mrs. Smith are concerned the fetus may have CF. They have come to you for prenatal diagnosis. You screen the
Smiths for the 25 most common CF mutations, but they do not have any of these mutations. You conclude they are carriers of rare CF mutations. Fortunately, there is a microsatellite marker very tightly linked (theta = 0.00) to the CF-causing gene. You obtain DNA from all the surviving
family members and the fetus (via CVS) and genotype them with respect to this linked marker.

The corresponding alleles are shown below:

Based on these results, what is the chance that the fetus has CF?

A. 0
B. 1/4
C. 1/2
D. 3/4
E. 1

Answer 35

The correct answer is E.

Question 36

What is the approximate risk that the woman indicated by the arrow in the pedigree below will have a son with the X-linked recessive lethal disorder that affects her brother?

A. 0.50
B. 0.25
C. 0.10
D. 0.05
E. 0.01

Pedigree: 3 generations

I Couple (Male & Female)

II 4 sons (3 unaffected, 1 affected), 1 daughter (unaffected)

III 1 son and 1 daughter (unaffected children of the daughter in II)

Answer 36

Bayes it out… Twice… –> The correct answer is D.

Question 37

An infant is noted to have ulnar deficiency. Based on this finding, which of the following syndromes is most likely?

CHARGE syndrome
Cornelia de Lange syndrome Kabuki syndrome
Pallister-Hall syndrome

Answer 37

Cornelia de Lange syndrome

Question 38

What autosomal recessive form of long QT syndrome includes sensorineural hearing loss?

Dravet
Timothy
Jervell and Lange-Nielsen
Alport

Answer 38

Jervell and Lange-Nielsen

Question 39

Pathogenic variants (mutations) in which gene are most associated with hereditary diffuse gastric cancer?

APC
BRCA1
CDH1
EPCAM

Answer 39

CDH1

Question 40

A child has severe, autosomal recessive neonatal disorder. What’s the chance his healthy 5 year-old sister is a carrier?

5% 25% 50% 67%

Answer 40

67%

Question 41

A woman has an FMR1 allele with 120 trinucleotide repeats (FMR1 is the Fragile X gene). What best describes this allele?

Normal allele
Intermediate allele Premutation allele
Full mutation allele

Answer 41

Premutation allele

Reminder:

Normal allele: ~5-44 repeats Intermediate allele: ~45-54 repeats
Premutation allele: ~55-200 repeats
Full mutation allele: >200 repeats