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200
1. The answer is (C).
They are first cousins once removed because the father of the male
member of the couple is the female member’s first cousin.
2. The answer is (C).
The coefficient of relationship (COR) between the couple is
1/32
1/32 1/16 because there are 6 individuals in the path from the male member of
the couple to the female member of the couple through both of the male’s great grandpar-
ents. Since COR
1/2
n
1
, it is 1/2
5
for each member of the couple or 1/32. When the two
are added, the result is 1/16. Since the Coefficient of Inbreeding (COI) is (COR)1/2, the COI
for this couple is (1/16)1/2 or 1/32.
3. The answer is (C).
First cousins are third-degree relatives.
4. The answer is (A).
The risk of bringing rare recessive genes together increases when there is
consanguinity because there is an increased chance that family members will share a
mutated gene already present in the family.
5. The answer is (B).
The risk for birth defects in first cousin matings has been empirically
derived to be roughly double that of the general population.
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201
1.
Which of the following are multifactorial
disorders?
(A)
Marfan syndrome, neurofibromatosis
(B)
Klinefelter syndrome, Turner syndrome
(C)
diabetes, most cancers
(D)
cystic fibrosis, sickle cell anemia
2.
Which of the following is a known envi-
ronmental factor in the development of a
cancer?
(A)
HPV
(B)
BCR
(C)
BRCA1
(D)
Rb1
3.
Certain combinations of chromosomes in
Robertsonian translocations carry a risk for
the carriers of these combinations to have
abnormal children because the possible tri-
somies that can result are viable (can be
born alive). Other combinations carry little
or no risk for abnormal children, but can
result in what is perceived as infertility
because abnormal conceptions may not be
recognized before they spontaneously abort.
Which one of the following Robertsonian
translocations in a carrier confers the great-
est risk for having an abnormal child?
(A)
t(14;21)
(B)
t(14;15)
(C)
t(15;15)
(D)
t(22;22)
4.
A couple has just had a third miscarriage.
They have had no successful pregnancies. A
review of the couple’s family histories reveals
that the husband’s mother had two miscar-
riages, and the husband’s sister has one
child, but has had two miscarriages. The
couple still wishes to have children. Which of
the following is the best recommendation for
how the couple should proceed?
(A)
The couple should consider adoption.
(B)
The couple should be tested for Fragile X.
(C)
The couple should have cytogenetic
studies performed.
(D)
The couple should be tested for cystic
fibrosis carrier status.
5.
Fragile X syndrome is one of the most
common causes of mental retardation in
humans. It generally acts like an X-linked
recessive disease, but some males do not
have the disease yet they can pass it on, and
some females are affected. The cause of the
disease explains these observations. Fragile
X syndrome is caused by which one of the
following mechanisms?
(A)
a deletion of the Prader-Willi/Angelman
gene on the father’s X chromosome
(B)
a triplet repeat expansion
(C)
chromosome breakage
(D)
having two X chromosomes
6.
Which one of the following is usually asso-
ciated with remission in chronic myeloge-
nous leukemia (CML)?
(A)
acquisition of the 9;22 translocation
(B)
appearance of the derivative chromo-
some 22 (Philadelphia chromosome)
(C)
disappearance of the derivative
chromosome 22 (Philadelphia
chromosome)
(D)
acquisition of massive hyperdiploidy
Use the following pedigree for questions 7 and 8.
Heidi
Key
d. 92
78
d. 39
d. CA
60
25
Br
Ov
Breast
cancer
Ovarian
cancer
42
Lila
Br
Ov
32
40
Br
36
Br
Br
Sylvia
Ov
Beverly
Cal
Tom
d. natural
causes
Hazel
d. “ female CA”
d. 50
LWBK274-COMP_201-227.qxd 06/02/2009 04:56 PM Page 201 Aptara
Heidi, age 25 and healthy, is concerned about
her paternal family history of breast cancer.
Her mother’s side is noncontributory (no his-
tory of cancer). Heidi’s paternal aunt, Sylvia,
was diagnosed with breast cancer at 36 and
died at 39. This aunt’s daughter, Lila, was
diagnosed with ovarian cancer at 40 and
breast cancer at 32. She is currently in remis-
sion at 42. Heidi’s paternal grandmother,
Hazel, died of “female cancer” at 50. Her
grandfather, Tom, died of natural causes at
92. She has one healthy aunt, Beverly, age 78.
Her father, Cal, is alive and well at 65.
7.
Who is the ideal person to have BRCA
testing first in this family?
(A)
Heidi
(B)
Lila
(C)
Beverly
(D)
Cal
8.
Regarding BRCA testing, which one of the
following statements applies?
(A)
Risks of BRCA testing include psycholog-
ical distress, change in family dynamics,
and a false sense of security if negative.
(B)
If Heidi has a BRCA mutation, she has a
100% risk for breast cancer.
(C)
Her only preventative option is mastec-
tomy if she is BRCA positive.
(D)
If Heidi has a BRCA mutation, each of her
future children would have a 25% risk to
inherit this from her.
9.
Cytogenetic changes in hematological
cancers, such as leukemia, generally act by
which one of the following mechanisms?
(A)
activation of proto-oncogenes
(B)
activation of tumor suppressor genes
(C)
deletion of proto-oncogenes
(D)
switching off proto-oncogenes
10.
Which one of the following disorders has
a 100% lifetime cancer risk if untreated
(100% penetrance)?
(A)
FAP (familial adenomatous polyposis)
(B)
HNPCC (hereditary non-polyposis col-
orectal cancer)
(C)
hereditary breast and ovarian cancer
(BRCA1 and BRCA2)
(D)
hereditary melanoma
11.
Which disorder conveys up to a 40% life-
time risk of ovarian cancer and a 6% risk for
male breast cancer?
(A)
FAP (familial adenomatous polyposis)
(B)
HNPCC (hereditary non-polyposis col-
orectal cancer)
(C)
hereditary breast and ovarian cancer
(BRCA1 and BRCA2)
(D)
hereditary melanoma
12.
Which one of the following is an example
of a good screening test?
(A)
tandem mass spec testing for phenylke-
tonuria (PKU)
(B)
DNA sequence testing for BRCA1 and 2
(C)
multiple mutation testing for cystic
fibrosis carrier status
(D)
multiple mutation testing for Marfan
syndrome
13.
Rami and Jillian have a son, Christian,
who is newly diagnosed with autism by a
developmental pediatrician. Jillian is preg-
nant with her second child, a male, as deter-
mined by ultrasonography. In order to deter-
mine recurrence risk, she brings the child to
you, the medical geneticist. Regarding your
management and counseling, which one of
the following best represents your response
to the couple?
(A)
You counsel them that autism is always
genetic and recurrence risk is 100%.
(B)
You start by drawing Christian’s blood for
chromosome analysis and Fragile X syn-
drome.
(C)
If chromosome analysis and Fragile X
testing is normal, you tell them their
child has no chance to have autism.
(D)
You tell them their new child should be
fine as long as he does not get any child-
hood vaccines or eat food with gluten,
because autism is entirely due to those
environmental factors.
14.
The hallmarks of a hereditary cancer syn-
drome include which of the following?
(A)
increased incidence of multiple and
bilateral tumors
(B)
late age of onset, i.e., postmenopausal
(C)
transmission through mothers only
(D)
autosomal recessive inheritance
usually
15.
A strong environmental component to a
trait is expected when which one of the fol-
lowing applies?
(A)
concordance is almost equal between
monozygotic and dizygotic twins
202
Board Review Series Genetics
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21.
In autosomal dominant and sex-linked
diseases that are genetic lethals (individuals
die before they can reproduce), the source of
the disease gene in the population is which
one of the following?
(A)
carriers of the disease gene
(B)
male carriers of the disease gene
(C)
female carriers of the disease gene
(D)
new mutations
22.
Which one of the following diseases is
autosomal recessive?
(A)
Huntington disease
(B)
Rett syndrome
(C)
Duchenne muscular dystrophy
(D)
Sickle cell disease
(E)
Fragile X syndrome
23.
In which disease does triplet repeat
expansion occur during male gametogene-
sis?
(A)
Huntington Disease
(B)
Rett syndrome
(C)
Duchenne muscular dystrophy
(D)
Sickle cell disease
(E)
Fragile X syndrome
24.
Symptoms of this disease include a his-
tory of developmental regression, mental
retardation, and characteristic hand move-
ments in affected females.
(A)
Huntington disease
(B)
Rett syndrome
(C)
Duchenne muscular dystrophy
(D)
Sickle cell disease
(E)
Fragile X syndrome
25.
Symptoms in affected males with this dis-
ease include large calves, Gower maneuver,
and greatly elevated levels of creatine kinase.
(A)
Huntington disease
(B)
Rett syndrome
(C)
Duchenne muscular dystrophy
(D)
Sickle cell disease
(E)
Fragile X syndrome
26.
Which one of the following diseases is a
common cause of inherited mental retarda-
tion in males?
(A)
Huntington disease
(B)
Rett syndrome
(C)
Duchenne muscular dystrophy
(D)
Sickle cell disease
(E)
Fragile X syndrome
Comprehensive Examination
203
(B)
there is a large difference in concordance
between monozygotic and dizygotic
twins
(C)
monozygotic concordance is close to 1.0
(D)
dizygotic concordance is close to 1.0
16.
Regarding type 1 and type 2 diabetes,
which one of the following statements
apply?
(A)
Type 2 diabetes has a stronger genetic
component than type 1.
(B)
The recurrence risk for type 2 diabetes is
minimal (
1%) for a first-degree relative;
first-degree relatives would not benefit
from earlier screening.
(C)
Type 1 diabetes is more common than
type 2 diabetes.
(D)
Type 2 diabetes has a minimal environ-
mental component.
17.
Which one of the following tests provides
the most benefits to a patient?
(A)
testing for BRCA1 and 2 mutations
(B)
Huntington disease testing for triplet
repeat number
(C)
testing for adenomatous polyposis coli
mutations
(D)
testing for cystic fibrosis carrier status
18.
All 50 states have newborn screening for
which of the following?
(A)
PKU, galactosemia, hypothyroidism
(B)
all biochemical disorders
(C)
hemoglobinopathies
(D)
cystic fibrosis
19.
The incidence of Aarskog syndrome, an
X-linked recessive disorder, is approximately
1 in 20,000 affected males. What is the fre-
quency of carrier females?
(A)
1 in 70
(B)
1 in 140
(C)
1 in 7,000
(D)
1 in 10,000
20.
When indications for Fragile X testing are
present in a patient (autism, mental retarda-
tion [MR], family history of MR in males),
which one of the following tests should also
be done?
(A)
testing for Huntington disease
(B)
cytogenetic testing
(C)
testing for CF carrier status
(D)
testing for phenylketonuria (PKU)
LWBK274-COMP_201-227.qxd 06/02/2009 04:56 PM Page 203 Aptara
27.
Hillary comes to your preconception
genetic clinic for a personal history of
Tetralogy of Fallot (a conotruncal congenital
heart defect). Hillary’s father was born with a
heart defect, has immunity problems, and
schizophrenia. Hillary’s brother has cleft
palate and a heart defect as well. Hillary has
tested positive for the microdeletion of
22q11.2 by FISH (DiGeorge syndrome). What
is the best estimate of the recurrence risk for
a future pregnancy?
(A)
2–3% (multifactorial risk of recurrence)
(B)
25%
(C)
50%
(D)
100%
The following pedigree applies to next question.
28.
Baby John has been diagnosed with mul-
tiple congenital anomalies shortly after birth
and there is no prior family history of abnor-
malities. Of the following, which one is the
most likely explanation for the clinical find-
ings?
(A)
autosomal dominant disease
(B)
X-linked dominant disease
(C)
chromosome abnormality
(D)
mitochondrial disease
29.
Which one of the following is NOT a syn-
drome for which fluorescent in situ
hybridization (FISH) is the primary test?
(A)
Williams syndrome
(B)
Prader-Willi syndrome
(C)
Di George syndrome
(D)
Cri-du-chat syndrome
30.
Regarding the classic autosomal reces-
sive conditions, which of the following state-
ments applies?
(A)
Pregnant women with PKU should not
stay on their low phenylalanine diet dur-
ing the pregnancy.
(B)
People with sickle cell trait are sickly and
need frequent blood transfusions.
John
(C)
A negative cystic fibrosis carrier screen
lowers a person’s carrier risk to zero.
(D)
Tay-Sachs disease causes progressive
neurologic and physical deterioration
until death around 5 years of age.
The following table applies to the next question.
The incidence of isolated sacral appendages,
a multifactorial disorder, varies worldwide
and is more common in North Carolina. This
table gives approximate recurrence risks (%)
in relation to population incidence.
204
Board Review Series Genetics
Population Incidence
United North
France
States
Carolina
Individual 1/1,000
1/500
1/200
Affected
One sibling
2%
3%
5%
Two siblings
8%
10%
12%
One second-
1%
1%
2%
degree relative
One third-
0.5%
0.5%–1%
1%
degree relative
31.
In your North Carolina genetics clinic, a
couple comes in for preconception counsel-
ing. Their first child had a sacral appendage
and no other birth defects. What is the recur-
rence risk for their next child to have this
birth defect?
(A)
5%
(B)
3%
(C)
2%
(D)
1%
32.
Iris and Toby are considering pregnancy
for the fifth time. They already have four
girls, all healthy and normal appearing. Toby
and his mother have Crouzon syndrome, an
autosomal dominant form of craniosynosto-
sis (premature fusion of the skull bones) with
a penetrance of 100%. What is the risk for the
fifth child to be affected?
(A)
0%
(B)
25%
(C)
50%
(D)
100%
The following pedigree applies to questions 33–35.
1
I
II
1
Cystic fibrosis
2
2
P
Key
3
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