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1.
Which one of the following is the test with
the highest sensitivity?
(A)
identifies 80% of those with the disease
and 95% of those without the disease
(B)
identifies 90% of those with the disease
and 80% of those without the disease
(C)
identifies 95% of those with the disease
and 70% of those without the disease
(D)
identifies 99% of those with the disease
and 60% of those without the disease
2.
The positive predictive power of the test in
question 1 is which one of the following?
(A)
65%
(B)
71%
(C)
86%
(D)
92%
3.
Population genetic screening for
Huntington disease does not conform to the
principles of genetic screening because of
which of the following?
(A)
The condition cannot be effectively
treated.
(B)
It is an adult onset disease.
(C)
Test results do not contribute to
informed reproductive choices.
(D)
Prenatal diagnosis is not available for this
disease.
4.
Which one of the following tests is offered
to virtually all pregnant women in the United
States?
(A)
chorionic villus sampling
(B)
ultrasonography
(C)
amniocentesis
(D)
cordocentesis
5.
Which one of the following best describes
neonatal genetic screening in the United
States?
(A)
All 50 states perform neonatal genetic
screening.
(B)
All 50 states perform neonatal genetic
screening for the same disorders.
(C)
All 50 states perform neonatal testing for
cystic fibrosis.
(D)
All 50 states perform neonatal genetic
testing for Tay-Sachs disease.
6.
An increased probability of Down syn-
drome is indicated by which one of the fol-
lowing maternal screening results?
(A)
low AFP, low unconjugated estriol, and
high HCG
(B)
low AFP, high unconjugated estriol, and
high HCG
(C)
low AFP, high unconjugated estriol, and
low HCG
(D)
low AFP, low unconjugated estriol, low
HCG
7.
Genetic testing for which one of the fol-
lowing may result in the prevention of dis-
ease in the individual tested?
(A)
Huntington disease
(B)
cystic fibrosis
(C)
Duchenne muscular dystrophy
(D)
familial adenomatous polyposis
8.
The major barrier to population cystic
fibrosis carrier screening has been which
one of the following?
(A)
The mutations responsible for the dis-
ease have not been identified.
(B)
The technology to identify mutations in
the gene did not exist.
(C)
Heterozygotes in various ethnic groups
could not be identified.
(D)
There are a large number of mutations
responsible for the disease and they vary
by ethnic group.
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1. The answer is (D).
Sensitivity is the ability to identify affected individuals and is measured
as the proportion of true positives. The identity of 99% of those with the disease gives this
test the highest sensitivity.
2. The answer is (B).
The sensitivity (99%) divided by the sensitivity (99%) plus the percentage
of false positives (40%) is 71%.
3. The answer is (A).
Huntington disease currently has no treatment and is invariably fatal.
Test results can inform couples about their risk of having a child with Huntington disease
so that informed reproductive decisions can be made. Prenatal diagnosis is available for
the disease.
4. The answer is (B).
Ultrasonography is offered to virtually all women in the United States at
12 weeks of gestation.
5. The answer is (A).
Not all states perform the same genetic screening tests but all states per-
form newborn screening for galactosemia, phenylketonuria, congenital hypothyroidism,
and sickle cell anemia.
6. The answer is (A).
A low alpha-fetoprotein value, along with low unconjugated estriol and
high human chorionic gonadotropin values in the maternal serum indicate an increased
probability of Down syndrome in a fetus.
7. The answer is (D).
Identification of a mutation in the APC gene would indicate that
increased monitoring of the intestinal epithelium is warranted in that individual. Any
polyps identified that could potentially progress to a malignancy would be removed.
8. The answer is (D).
There are over 1,000 mutations responsible for cystic fibrosis and the
ones that are responsible for most of the cases vary by ethnic group. The mutations respon-
sible for cystic fibrosis are well characterized and new technologies may eventually allow
for population screening for cystic fibrosis.
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Consanguinity is mating with a blood relative where there is at least one common ancestor no
more remote than a great-great-grandparent.
Incest
is mating between a parent and child or
between brother and sister (first-degree relatives). Consanguineous marriage is common in
many parts of the world and many states within the United States allow first-cousin marriages.
For example, in the Indian population, consanguineous marriage between an uncle and niece
(second-degree relatives) occurs. In the Arab population, consanguineous marriage between
first cousins (third-degree relatives) who are the children of two brothers occurs.
A. Consanguinity Increases the Incidence of Rare Autosomal Recessive Disorders.
B.
The mating of first cousins provides the exact conditions that allow rare recessive disorders
to manifest. The mating of first cousins almost doubles incidence of birth defects compared
to the general population.
C.
Consanguinity slightly increases the incidence of multifactorial inherited disorders.
D. Coefficient of Relationship (COR).
COR is the proportion of genes in common between two
related individuals. COR is described by the equation below.
E. Coefficient of Inbreeding (COI) or Homozygous by Descent.
COI is the probability that an indi-
vidual is homozygous at a locus as a result of consanguinity in his or her parents. COI is
described by the equation below.
F. Summary Table of COI (Table 18-1).
G. Example of Consanguinity (Figure 18-1).
Paula is a carrier of CFN (congenital Finnish nephro-
sis), a rare autosomal recessive kidney disease. If she mates with her first cousin Simon (a
cousin through her maternal uncle), what is the chance he also carries the abnormal gene?
1. How many individuals are in the pedigree path?
Begin with Paula and ascend the pedigree
path to one of the common ancestors (in this example it is Paula’s grandfather). Then
COI
(COR)1/2
COR
(1/2)
n
1
where n
number of
individuals in the path
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Board Review Series Genetics
descend the pedigree to Simon. Counting Paula and Simon, there are
5 individuals in this
path
(Note the numbering on the pedigree).
Therefore n
5
.
2. What is the COR between Paula and Simon through the grandfather and grandmother?
a.
Calculate the COR between Paula and Simon through the grandfather: COR
(1/2)
n
1
(1/2)
5
1
(1/2)
4
1/16 (6%). Consequently, there is a 6% chance that Simon has inher-
ited the gene if it was passed through the grandfather.
b.
Calculate the COR between Paula and Simon through the grandmother (because they
also share their grandmother as a common ancestor, you must calculate the COR for
her the same way): COR
(1/2)
n
1
(1/2)
5
1
(1/2)
4
1/16 (6%).
Consequently, there
is a 6% chance that Simon has inherited the gene if it was passed through the grand-
mother.
c.
Calculate the final COR for first cousins: Add the common ancestors’ COR’s: 1/16
1/16
1/8 (12%). Therefore, the final COR for first cousins is 1/8 (12%). This can be interpreted
as a 1/8 (12%) chance that Simon is a carrier of the abnormal gene.
3. If Paula and Simon have a child that is affected with CFN, what is the chance that the child
inherited both abnormal alleles from a common ancestor?
The COR for first cousins is 1/8. So,
COI
(COR) 1/2 (1/8) (1/2) 1/16 (6%). This can be interpreted as a 1/16 (6%) chance
that the CFN affected child inherited both abnormal alleles from a common ancestor.
t a b l e
18-1
Table of COI
Relationship
Degree of Relationship
COR
COI
Parent-child
First degree
1/2 (50%)
1/4 (25%)
Brother-sister
First degree
1/2 (50%)
1/4 (25%)
Uncle-niece
Second degree
1/4 (25%)
1/8 (12%)
First cousins
Third degree
1/8 (12%)
1/16 (6%)
Second cousins
Fifth degree
1/32 (3%)
1/64 (1.5%)
Simon
I
II
III
1
2
3
4
5
3
Paula
FIGURE 18-1: A pedigree of consanguinity.
The numbers indicate number of individuals in the pedigree path. You can
count through Paula’s grandfather (3) or Paula’s grandmother (3). In both cases, there are 5 individuals in the path.
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Use this pedigree for the next two questions:
1.
How is this couple related?
(A)
uncle-niece
(B)
first cousins
(C)
first cousins once removed
(D)
second cousins
2.
What is the COI?
(A)
1/8
(B)
1/16
(C)
1/32
(D)
1/64
3.
A marriage between first cousins would be
a marriage to which one of the following?
(A)
a first-degree relative
(B)
a second-degree relative
(C)
a third-degree relative
(D)
a fourth-degree relative
4.
Consanguinity increases the risk for which
one of the following?
(A)
autosomal recessive disorders
(B)
autosomal dominant disorders
(C)
mitochondrial disorders
(D)
X-linked dominant disorders
5.
The mating of first cousins does what to
the incidence of birth defects compared to
the general population?
(A)
nothing
(B)
doubles the risk
(C)
triples the risk
(D)
quadruples the risk
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