Файл: Genetics [BRS].pdf

41. The answer is (C).

In an X-linked recessive condition, males will be affected and carrier

females will not. Because sons do not receive an X chromosome from their father, only
daughters have a chance of becoming carriers. 

42. The answer is (B).

Autosomal recessive conditions generally appear in a family without a

prior family history. The parents are unaffected obligate carriers.

43. The answer is (A).

In autosomal dominant mutations, there is a 50% chance of passing on

the mutation. Autosomal recessive inheritance is not likely since these conditions are
rare so the chance that the mother is a carrier of an autosomal recessive mutation is very
small. Because a father cannot pass on an X chromosome to his sons, passing on X-linked
conditions to the sons is not possible.

44. The answer is (B).

It is not likely that daughters would be affected with X-linked recessive

disorders. Autosomal and X-linked dominant disorders can affect both sexes in any gen-
eration. All children of a mother with a mitochondrial condition would be affected. 

45. The answer is (A).

When multiple siblings are affected with an autosomal dominant or X-

linked disease and the parents are unaffected with no family history, germline mosaicism
is the likely explanation. Mutations of different genes that cause the same phenotype is
locus heterogeneity, an affected individual having more severe disease than a sibling is
an example of variable expression, and penetrance is an all or none phenomenon where
an individual may or may not express a phenotype, even though the disease genotype is
present. 

46. The answer is (B).

Amniocentesis is typically done from 15 to 18 weeks of gestation and

has a very low risk of complications.

47. The answer is (C).

Taking a blood sample from the umbilical cord allows management of

Rh incompatibility as well as the diagnosis of hematological abnormalities. 

48. The answer is (B).

CVS is typically done earlier than amniocentesis, at 10–12 weeks.

However, it carries a larger risk for complications, most notably limb defects. 

49. The answer is (C).

An AFP assay can be performed on amniotic fluid to determine if the

AFP is elevated. This could be an indication that a neural tube defect is present. This test
cannot be performed with CVS. Cordocentesis is useful for assessing hematological sta-
tus or infection and the blood obtained can be used for karyotyping. Screening tests are
useful for screening at risk populations but the risk is not eliminated if the test is nega-
tive. 

50. The answer is (E).

When genes producing the same phenotype are found at different loci,

this is called locus heterogeneity. These genes are generally not linked. Synteny refers to
genes on the same chromosome, which do not usually cause the same phenotype and
are usually not linked. Allelic heterogeneity refers to the situation when different muta-
tions at the same locus cause the same phenotype. 

51. The answer is (B).

These findings are the hallmark of Tay-Sachs disease, which is a degra-

dation pathway disorder. The disease progresses from normal at birth to an early death
because of the buildup of a ganglioside in neurons due to the inability of a lysosomal
enzyme to degrade it. 

52. The answer is (D).

Metabolic diseases are usually due to the failure of an enzyme in a bio-

chemical pathway and are not associated with growth disorders. All the other choices are
clinical findings in metabolic disorders. 

53. The answer is (C).

The findings described with the history are generally seen in metabolic

disorders, which are not associated with cytogenetic abnormalities. Performing a chro-
mosome study would not be helpful in this instance. 

54. The answer is (C).

Because the Prader-Willi region of chromosome 15 is imprinted, uni-

parental disomy for the maternal chromosome 15 would mean that there are two copies

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of the maternal region of chromosome 15 but no copies of the paternal region resulting
in Prader-Willi syndrome. 

55. The answer is (D).

More severe disease with an earlier age of onset in succeeding genera-

tions is called anticipation. Anticipation can also be observed in diseases with triplet
repeat expansions such as Fragile X syndrome. 

56. The answer is (D).

All cancers have a genetic component but most cancers are multifacto-

rial diseases. Only a small group of cancers are inherited. Chromosome abnormalities of
all kinds, not just translocations, are associated with many hematological disorders and
solid tumors, but in many cases, chromosome aberrations are related to progression of
the cancer and not necessarily the cause. 

57. The answer is (A).

Retinoblastoma is inherited in an autosomal dominant fashion. The

inherited mutated tumor suppressor gene is considered the first “hit” in the progression to
a malignant tumor but it takes a mutation in the other allele for the cancer to occur. So, as
in the case of autosomal recessive diseases, both mutated alleles must be present before
the disease occurs, but in retinoblastoma, the second mutation is acquired, not inherited. 

58. The answer is (B).

Even though a diagnosis of trisomy 21 can often be made based on the

phenotype alone, cytogenetic analysis can confirm the diagnosis in those cases as well as
the ones where the diagnosis may not be as obvious. It is also important to rule out the
possibility of Down syndrome due to a Robertsonian translocation, as this may have
reproductive ramifications for the family. 

59. The answer is (C).

Humans have approximately 30,000 genes versus around 19,000 for 

C. elegans but have the most non-coding DNA of any organism examined to date.
Humans have 46 chromosomes but one species of tree frog has 48 chromosomes and
carp have 100 chromosomes. 

60. The answer is (B).

In the autosomal dominant Huntington disease, both homozygotes

and heterozygotes will have the disease and there is no difference in clinical course with
either genotype. In small populations founded by a few individuals, some genotypes may
be over-represented than would be expected by chance. If individuals with the
Huntington gene had more descendants than those with other genotypes, the frequency
of the Huntington gene would be expected to increase in the population.

61. The answer is (D).

In X-linked recessive disorders, the frequency of the gene is the same

as the frequency of the disease. Because the disease frequency is 1/20,000, this equals
0.00005 and that is the gene frequency as well. 

62. The answer is (B).

If a balanced reciprocal translocation involves very large segments of

the chromosomes, unbalanced outcomes in a conception may be lethal. Sometimes
development ends so soon after conception that the couple may not even know that they
were pregnant. Perceived infertility would result. There is still a chance of having normal
children and the risk for an abnormal child with this couple seems to be small. If they
have managed to conceive, none of the unbalanced conceptions have apparently devel-
oped much beyond conception. 

63. The answer is (C).

A group of birth defects with a single cause is a syndrome. In an associ-

ation, two or more traits occur together more often than by chance but do not necessary
have the same cause. In a deformation, the normal development of a body part is altered
by mechanical forces. A disruption is a defect in a morphological structure due to the fail-
ure of a normal developmental process. 

64. The answer is (A).

Allelic heterogeneity can cause the same disease or clinically distinct

diseases by different mutations at the same locus. 

65. The answer is (B).

Because the Prader-Willi/Angelman locus is imprinted, a deletion of

that region on the paternal chromosome 15 will cause Prader-Willi syndrome and a dele-
tion of that region on the maternal chromosome 15 would cause Angelman syndrome.

Answers and Explanations

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66. The answer is (A).

There is a 50% or 1/2 chance that your patient inherited the mutation,

a 50% or 1/2 chance that she will pass it on, and a 50% or 1/2 chance that the child will be
a male and thus affected. So, 1/2

 1/2  1/2  1/8 chance to have an affected fetus.

67. The answer is (A).

Low AFP, high HCG, and low uE3 values in a triple screen test indicates

an elevated risk for Down syndrome. Amniocentesis with karyotyping is a very low risk,
extremely accurate test for detecting Down syndrome. 

68. The answer is (B).

FISH is the definitive test for microdeletions. Klinefelter and Turner

syndromes can be detected with conventional chromosome analysis. FISH is not the test
of choice for the other disorders listed. 

69. The answer is (A).

A fetus with anencephaly is not viable. Neural tube defects are multi-

factorial and not associated with the mother’s age at conception. A high maternal serum
AFP indicates an increased risk for a fetal open neural tube defect. 

70. The answer is (B).

In meiosis, inverted chromosomes have to form a loop to pair up with

the normal homolog. If crossing over occurs in the inversion loop, unbalanced recombi-
nant chromosomes with duplications and deletions can result.

71. The answer is (C).

Approximately 90% of 45,X conceptions spontaneously abort. Those

that survive to birth are females with Turner syndrome. Individuals with Turner syn-
drome do not have a male phenotype, they are not mentally retarded, and there is no
association between Down syndrome and Turner syndrome.

72. The answer is (A).

When mutations at different loci result in the same phenotype, that

constitutes locus heterogeneity. Allelic heterogeneity occurs when mutations at the same
locus produce the same disease or clinically distinct diseases. 

73. The answer is (A).

The 9;22 translocation fuses the ABL and BCR proto-oncogenes, creat-

ing a chimeric or fusion gene in which both proto-oncogenes are activated. 

74. The answer is (E).

A brother is a first-degree relative. First cousins and great-grandchil-

dren are third-degree relatives. A second cousin would be a fourth-degree relative. Half-
siblings are second-degree relatives. 

75. The answer is (B).

The risk that Mrs. X’s mother inherited the mutation is 50% or 1/2. The

risk that Mrs. X inherited the mutation from her mother is 50% or 1/2. The chance that
Mrs. X will pass on the mutation to the fetus is 50% or 1/2. The risk that the male fetus
will have the mutation is 50%. So the risk is 1/2

 1/2  1/2  1/8 that the fetus will have

hemophilia A.

76. The answer is (B).

Amniocentesis is the test of choice for detecting, through chromosome

analysis, Down syndrome. The triple screen is generally done outside the optimal time
for CVS and CVS carries a higher risk for complications. Ultrasonography can pick up
some signs of Down syndrome but is not as accurate as chromosome analysis. PGD does
not apply as the patient is already pregnant. 

77. The answer is (C).

In an autosomal dominant syndrome, a first-degree relative would

have a 50% chance of inheriting the mutation, second-degree relatives a 50% chance of
the 50% risk the first-degree relative has or 25%, and a third-degree relative would have a
50% chance of the 25% risk the second-degree relative has or 12.5%. 

78. The answer is (C).

In an X-linked recessive disorder, the possible outcomes would be: a 1/4

chance of having a female who is a carrier, a 1/4 chance of having a female who is not a
carrier, a 1/4 chance of having a male who is unaffected, and a 1/4 chance of having a
male who is affected. 

79. The answer is (A).

The number of individuals who are truly affected is the proportion of

people in the population who have the null mutation, 0.003, so 0.003 

 20,000  60 peo-

ple in the population have the null mutation. Because the test has a sensitivity of 95%, it
will detect 95% of those who are truly positive, or 0.95 

 60  57 of the people who are

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really affected will be detected by the test. The test has a specificity of 99%, so it will iden-
tify 99% of those who are negative for the null mutation. The remainder, 0.1 

 20,000  200

people will be identified as positive for the null mutation. So the number of people the test
will indicate are positive are the 57 the test correctly identifies as positive plus the 200 peo-
ple the test indicates are positive, or 200 

 57  257 people the test would call positive. 

80. The answer is (C).

Since MSAFP is offered in the second trimester, it is generally done

after the optimal time for chorionic villus sampling (CVS). An adjustment of seven days
in determining gestational age would not appreciably affect the MSAFP results. A woman
who delivers at age 35 or older is at an increased risk to have a child with Down syndrome
and other chromosome abnormalities and negative MSAFP results would not eliminate
that risk. A high MSAFP may indicate that there is an open neural tube defect so ultra-
sonography should be done to look for defects and amniocentesis should be offered to
determine if a chromosome abnormality is present. 

81. The answer is (E).

Because the development of multiple cancers in an individual is a rare

event, a proband with multiple cancers indicates that there are probably strong genetic
factors, consistent with familial cancers, involved in the development of the multiple
cancers.

82. The answer is (D).

In autosomal dominant diseases, homozygotes are rare so most of

those affected are heterozygotes. The frequency of the allele “p” is 0.0001. Because “p” is
very small, “q” is close to 1 and the frequency of heterozygotes, those affected, is 2pq or
2(0.0001)(1)

 0.0002. 

83. The answer is (C).

The carrier of a 14;14 translocation has no risk of having an abnormal

child due to the translocation because unbalanced conceptions are lethal and do not
develop much beyond conception. The pregnancies abort so early that the patient may
not know that she is pregnant. This will be perceived as infertility. She is, however, capa-
ble of having a normal child or a carrier like herself, who will also be phenotypically nor-
mal. 

84. The answer is (D).

Because no mitochondria can be passed on through the sperm, only

through the ovum, a father cannot pass on a mitochondrial mutation to any of his chil-
dren. 

85. The answer is (B).

The recurrence risk in multifactorial disorders is higher when there is a

more severe phenotype because the increased severity means that more of the compo-
nents that cause the phenotype are present. 

86. The answer is (B).

The risk to have an affected child in autosomal recessive disorders

when both parents are carriers is 25%. The chance of having a child who is not affected
and not a carrier is also 25%. The chance that a child will be an unaffected carrier of the
mutation is 50%. 

87. The answer is (B).

In an inversion, there are two breakpoints. The piece between the two

breakpoints flips over into the opposite direction, so the genes on that section are in
reverse order. 

88. The answer is (D).

An individual with a Robertsonian translocation who has a normal

phenotype will have 45 chromosomes because two of the chromosomes, in this case a 13
and a 21, have fused into one chromosome, thus lowering the total count to 45. An indi-
vidual with a Robertsonian translocation and 46 chromosomes has an additional copy of
one of the chromosomes involved in the translocation. In this case, the individual would
have an extra copy of either chromosome 13 or 21. If it was a copy of chromosome 13, the
individual would have a trisomy 13 phenotype. If the extra copy was chromosome 21, the
phenotype would be that of trisomy 21. A 45, X karyotype is found in Turner syndrome. A
47,XXY individual would have Klinefelter syndrome.

89. The answer is (D).

In the case of a 21;21 Robertsonian translocation carrier, both copies of

that individual’s chromosome 21 are translocated to each other to form one chromosome.

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At meiosis, the translocation 21;21 chromosome can only go to one daughter cell or the
other, so at the end of meiosis there will be, in females, either one ovum with two copies
of chromosome 21 in the translocated chromosome or an ovum with no copies of chro-
mosome 21. At fertilization, the sperm will donate one copy of chromosome 21 to the
conception and if the ovum contains the translocation 21;21 chromosome, there will be
three copies of chromosome 21 in the conceptus. If pregnancy is successfully completed,
the baby will have Down syndrome. Fertilization of an ovum with no copies of chromo-
some 21 will not proceed far since this is a lethal condition. 

90. The answer is (C).

Heart disease and diabetes are multifactorial diseases with both

genetic and environmental components. Robertsonian translocations are chromosomal
events, cystic fibrosis and sickle cell anemia are autosomal recessive diseases, and
Duchenne muscular dystrophy and hemophilia are X-linked recessive disorders.

91. The answer is (D).

Because that individual has only one X, a mutation on that X would

cause the disease in that individual. All the other individuals have two X chromosomes,
and because Duchenne muscular dystrophy is X-linked recessive, they would be carriers,
but not afflicted with the disease. 

92. The answer is (A).

In multifactorial diseases, there is often sex bias where one sex is more

frequently affected than the other. Most multifactorial diseases have a recurrence risk of
10%.

93

.

The answer is (C).

Penetrance is the percentage of those who actually have a disorder ver-

sus those who have the genotype but are not affected.

Because

Jim must have the

Marfan genotype but is not affected, then this constitutes non-penetrance for this disor-
der. Penetrance is all or none. In variable expressivity, a disorder may have degrees of
expression but the disorder phenotype is present to some degree. In allelic and locus het-
erogeneity, a disease phenotype is also present. 

94. The answer is (D).

The homeotic or HOX gene family plays a major role in early develop-

ment. Proto-oncogenes are involved in some aspects of later development but do not
having any role in spatial patterning. The delta F508 mutation is the most common one
in cystic fibrosis.

95. The answer is (A).

The risk of a chromosome abnormality begins to increase in women

who 35 or older. Paternal age does not carry an increased risk until age 50 or older and
that risk is mostly for single gene mutations. The karyotype of most miscarriages, about
50%, is normal and this does not increase the risk of a chromosome abnormality in sub-
sequent pregnancies. Cystic fibrosis cannot be diagnosed or carrier status established by
chromosome analysis.

96. The answer is (B).

A gene is transcribed, the messenger RNA is translated, and a protein is

synthesized.

97. The answer is (C).

If the inactivation of the normal X is skewed and a large number are

inactivated, there may be enough active copies of the mutated X chromosome to cause
some symptoms of disease. X-linked recessive diseases generally do not show variable
expressivity and are usually fully penetrant. 

98. The answer is (B).

The possible outcomes in an autosomal dominant disease with both

parents affected are: 1/4 will be homozygous, 1/2 will be affected, and 1/4 will be normal. 

99. The answer is (A).

In a pericentric inversion, the two breakpoints of the inverted segment

are on either side of the centromere, with one in the short arm and one in the long arm of
the chromosome. Because the breakpoints are rarely equidistant from the centromere,
inverting the piece containing it will place it in a different position on the chromosome. 

100. The answer is (B).

Because heterozygotes have some degree of protection against

malaria, they will more likely to survive to reproduce and pass on the sickle cell trait.
Those who do not have sickle cell trait are more likely to contract malaria and less likely

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