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1.
Which of the following is the risk that an
unaffected full sibling of a patient with cystic
fibrosis (CF) carries a mutated CF gene?
(A)
1 in 2
(B)
1 in 4
(C)
3 in 4
(D)
2 in 3
2.
What is III-1’s risk to be a carrier of Alport
syndrome, an X-linked recessive condition?
(A)
0
(B)
25%
(C)
50%
(D)
100%
3.
What is the risk that the child of a mother
with cystic fibrosis will be a carrier of the dis-
ease?
(A)
100%
(C)
50%
(B)
75%
(D)
25%
4.
Which pedigree best represents X-linked
dominant inheritance for a nonlethal condi-
tion?
(A)
pedigree A
(B)
pedigree B
(C)
pedigree C
1
2
I
1
2
1
2
II
III
5.
In X-linked recessive lethal disorders, the
mutant gene is not always inherited from a
carrier female (Haldane’s rule). What approx-
imate percentage of affected males is attrib-
utable to a new mutation?
(A)
100%
(B)
75%
(C)
66%
(D)
33%
6.
Mutations in different autosomal reces-
sively inherited genes may result in the
development of leukemia in Fanconi anemia
patients. Which of the following best
describes why this can happen?
(A)
locus heterogeneity
(B)
allelic heterogeneity
(C)
genotype-phenotype correlation
(D)
de novo mutations
(E)
variable expressivity
7.
A 15-year-old boy is referred to a genetics
clinic to rule out neurofibromatosis 1. He
reports having
25 café-au-lait spots and
has started getting lumps and bumps on his
skin since he hit puberty. During the family
history, he describes his brother as being
born with bowed legs and reports that he
died at age 12 from a tumor in his neck that
had been there since birth. He remembers
that his brother had some birthmarks, but
not nearly as many as he has. He does not
recall his parents having any birthmarks, but
they are not with him at the appointment.
Pedigree A
Pedigree B
Pedigree C
LWBK274-C04_26-44.qxd 06/02/2009 03:34 PM Page 40 Aptara
Chapter 4
Mendelian Inheritance
41
What inheritance pattern for the disease is
occurring in this family?
(A)
autosomal dominant
(B)
autosomal recessive
(C)
X-lined dominant
(D)
X-linked recessive
(E)
multifactorial
8.
In Marfan syndrome, the affected protein,
Fibrillin-1, is active in three parts of the
body: the aorta, the suspensory ligaments of
the lens, and the periosteum or connective
tissue. This is an example of which of the fol-
lowing?
(A)
germline mosaicism
(B)
reduced penetrance
(C)
variable expressivity
(D)
pleiotropy
(E)
locus heterogeneity
The following pedigree applies to questions
9 and 10.
John
9.
Baby John was diagnosed with achon-
droplasia shortly after birth. What inheri-
tance pattern should be discussed with the
parents?
(A)
autosomal dominant
(B)
autosomal recessive
(C)
X-linked dominant
(D)
X-linked recessive
(E)
multifactorial
10.
What is the recurrence risk for the couple
to have another child with achondroplasia?
(A)
50%
(B)
25%
(C)
3%–5%
(D)
1%–2%
(E)
0%
11.
Britney and Kevin have two healthy sons,
Preston and Jaden. Britney has a full brother,
Brian, with G6PD deficiency. Britney’s mom,
Lynne, has two brothers with G6PD defi-
ciency. Britney is currently 10 weeks preg-
nant by her new partner, Isaa. What is the
risk the current fetus has G6PD deficiency?
(A)
1/2
(B)
1/4
(C)
1/8
(D)
1/16
(E)
1/32
12.
Sally has a paternal uncle with hemo-
philia B, an X-linked recessive disease. Her
risk of having a child with hemophilia B is
best described as which of the following?
(A)
near 100%
(B)
near 0%
(C)
50% with all male children
(D)
50% for all children
13.
Joe’s brother has cystic fibrosis. What is
the risk that Joe is a carrier?
(A)
1/3
(B)
2/3
(C)
1/4
(D)
1/2
14.
Female carriers of X-linked recessive dis-
eases sometimes exhibit some symptoms of
the disease. The cause of this is which of the
following?
(A)
variable expressivity of the X-linked gene
(B)
mitochondrial inheritance
(C)
skewed X chromosome inactivation
(D)
incomplete penetrance of the X-linked
gene
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42
BRS Genetics
Using the following information, choose the
best answer to questions 15-18.
Alan has hemophilia A. His sister, Alice, has
one son, Blaine. Blaine also has hemophilia
A. Alan and his wife Annette have 2 children,
Bart and Barbara. Barbara has a daughter,
Cassie, and a son Chip. Cassie and Blaine are
married and have a son, Daniel, with hemo-
philia A. They are now expecting fraternal
twins, a boy and a girl.
15.
What is Barbara’s risk to be a carrier of
hemophilia A?
(A)
0%
(B)
25%
(C)
50%
(D)
75%
(E)
100%
16.
What is Cassie and Blaine’s daughter’s
(the fraternal twin) risk to be affected with
hemophilia A?
(A)
0%
(B)
25%
(C)
50%
(D)
75%
(E)
100%
17.
What is Cassie and Blain’s son’s (the fra-
ternal twin) risk to have hemophilia A?
(A)
0%
(B)
25%
(C)
50%
(D)
75%
(E)
100%
18.
How are Barbara and Blaine related?
(A)
first cousins
(B)
first cousins once removed
(C)
second cousins
(D)
second cousins once removed
19.
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
20.
In myotonic dystrophy, the severity of
the disease increases with each succeeding
generation. This phenomenon is called:
(A)
anticipation
(B)
incomplete penetrance
(C)
genomic imprinting
(D)
variable expressivity
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43
1. The answer is (D).
If the full sibling’s status was unknown, he would have a 1 in 4 risk of
being unaffected and not carrying a CF mutation gene, a 2 in 4 risk of being unaffected but
a carrier of a CF mutation and a 1 in 4 risk of having CF. Because he is unaffected, there are
3 possible independent outcomes. He now has a 1 in 3 chance of not carrying a mutated CF
gene, but a 2 in 3 chance of being a carrier of a CF mutation.
2. The answer is (C).
Because her mother is an obligate carrier of Alport syndrome, there is a
50% chance that she passed on the X chromosome with the mutation and a 50% chance
that she passed on the normal X chromosome.
3. The answer is (A).
The mother is homozygous for a CF mutation (aa) so she can only pass
along a mutated gene (a). The father is presumably homozygous for the normal gene (AA),
so he can only pass on a normal gene (A). Therefore, all their children will be heterozygotes
(Aa), or carriers of a CF mutation.
4. The answer is (C).
In Pedigree C, the condition appears in every generation in both sexes.
Pedigree A is a possibility, but only males are affected and Pedigree B the condition “skips”
a generation and only males are affected.
5. The answer is (D).
In lethal disorders, all the mutated genes are lost in each generation and
these represent a third of the alleles for that mutated gene. In a population at equilibrium,
the number of new mutations equals the number of genes lost, so that number of new
mutations replacing those lost is one-third, or 33%.
6. The answer is (A).
Because different genes (loci) can be involved in the development of
leukemia, there is locus heterogeneity.
7. The answer is (A).
Neurofibromatosis 1 (NF1) is an autosomal dominant disease with vari-
able expressivity. The family history and the clinical findings in the patient confirm the
diagnosis of NF1. The fact that the patient’s brother had it means that it probably was not
due to a new mutation. One of the parents would probably be found to have some mild
manifestation of the disease upon examination, as it is fully penetrant.
8. The answer is (D).
Pleiotropy is when a gene mutation produces diverse phenotypic events.
Marfan syndrome is one of the best examples of pleiotropy.
9. The answer is (A).
Achondroplasia is an autosomal dominant disease. There is no family
history because achondroplasia is often caused by a new mutation.
10. The answer is (E).
Because the cause of achondroplasia in John is a new mutation, it is
extremely unlikely to happen again so the risk is
0.
11. The answer is (C).
G6PD deficiency is X-linked. The risk that Britney received the mutation
from her mother Lynne, an obligate carrier, is 50% or 0.5. The chance that the fetus will be
a girl is 50% or
1
⁄
2
. The chance that the girl will be a carrier is 50% if the mother is a carrier.
So,
1
⁄
2
0.5
1
⁄
2
1
⁄
8
.
12. The answer is (B).
Because Sally’s father does not have hemophilia B, he does not have the
X chromosome with the mutated gene to pass on to Sally. Therefore, the risk for Sally to
have a child with hemophilia B is near 0.
13. The answer is (B).
Because Joe is unaffected, he can be a carrier or not be a carrier. He has a
1 in 3 chance of not being a carrier and a 2 in 3 chance of being a carrier.
14. The answer is (C).
If sufficient numbers of normal X chromosomes are inactivated, there
may not be enough of the normal gene product present for proper functioning. In these
LWBK274-C04_26-44.qxd 06/02/2009 03:34 PM Page 43 Aptara
cases, there may be a partial or complete disease phenotype due to the fact that the major-
ity of the gene product produced will be defective or nonfunctional.
15. The answer is (E).
Because Barbara’s daughter Cassie has a son with hemophilia A, Cassie
must have received the mutation from her mother. The mutation could not have come
from Blaine because he cannot pass on his X chromosome to his son. Both Barbara and
Cassie are obligate carriers.
16. The answer is (C).
Because Blaine has hemophilia A, he can only pass on an X chromosome
with the mutation. Cassie is an obligate carrier with one X chromosome carrying the muta-
tion and a normal X chromosome. The female fraternal twin can either receive a mutated X
chromosome from both parents and have hemophilia A, or receive the mutated X from
Blaine and a normal X from Cassie and be a carrier. The risk of being affected with hemo-
philia A is thus 50%.
17. The answer is (C).
Blaine can only pass on a Y chromosome to sons. Cassie can either pass
on the X chromosome with the mutation and her son will have hemophilia A, or pass on
the normal X chromosome, in which case her son would be normal and not affected with
hemophilia A. The risk of being affected with hemophilia A is thus 50%.
18. The answer is (A).
Alan is Barbara’s father and his sister Alice is Blaine’s mother. Alan is
Blaine’s uncle and his daughter Barbara is Blaine’s first cousin.
19. The answer is (B).
In Fragile X syndrome the triplet repeat expansion, CGG, must reach a
certain number of repeats before there is clinical manifestation of the disease. The repeat
expands with succeeding generations and eventually will reach the critical number. That is
why males without the disease can pass it on to subsequent generations where it appears
because the threshold number of repeats has been reached. Females with a high number
of repeats may also express some manifestations of the disease because of skewed X inacti-
vation.
20. The answer is (A).
Myotonic dystrophy is caused by a triplet repeat expansion that expands
with each succeeding generation. The larger the repeat, the earlier the onset and the more
severe the disease is. This phenomenon is called anticipation and differs from incomplete
penetrance and variable expressivity in that once the critical repeat threshold is reached,
the disease is manifested with severity depending on the number of repeats.
44
BRS Genetics
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