Chapter Six: Pedigree Analysis and Applications

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Chapter Six: Pedigree Analysis and Applications

COMPREHENSION QUESTIONS
*1.

What three factors complicate the task of studying the inheritance of human
characteristics?
(1) Mating cannot be controlled, so it is not possible to set up controlled mating
experiments.
(2) Humans have a long generation time, so it takes a long time to track
inheritance of traits over more than one generation.
(3) The number of progeny per mating is limited, so phenotypic ratios are
uncertain.

*2.

Describe the features that will be exhibited in a pedigree in which a trait is

segregating with each of the following modes of inheritance: autosomal recessive,
autosomal dominant, X-linked recessive, X-linked dominant, and Y-linked
inheritance.
Pedigrees with autosomal recessive traits will show both affected males and
females arising with equal frequency from unaffected parents. The trait often
appears to skip generations. Unaffected people with an affected parent will be
carriers.
Pedigrees with autosomal dominant traits will show both affected males and
females arising with equal frequency from a single affected parent. The trait does
not usually skip generations.
X-linked recessive traits will affect males predominantly and will be passed
from an affected male through his unaffected daughter to his grandson. X-linked
recessive traits are not passed from father to son.
X-linked dominant traits will affect both males and females and will be passed
from an affected male to all his daughters, but not to his sons. An affected woman
(usually heterozygous for a rare dominant trait) will pass on the trait equally to half
her daughters and half her sons.
Y-linked traits will show up exclusively in males, passed from father to son.

*3.

What are the two types of twins and how do they arise?
The two types of twins are monozygotic and dizygotic. Monozygotic twins arise
when a single fertilized egg splits into two embryos in early embryonic cleavage
divisions. They are genetically identical. Dizygotic twins arise from two different
eggs fertilized at the same time by two different sperm. They share, on the average,
50% of the same genes.

4.

Explain how a comparison of concordance in monozygotic and dizygotic twins can

be used to determine the extent to which the expression of a trait is influenced by
genes or environmental factors.
Monozygotic twins have 100% genetic identity, whereas dizygotic twins have 50%
genetic identity. Any trait that is completely genetically determined will therefore be
100% concordant in monozygotic twins and 50% concordant in dizygotic twins.

73 Chapter Six: Pedigree Analysis and Applications

Conversely, any trait that is completely environmentally determined will have the
same degree of concordance in monozygotic and dizygotic twins. To the extent that
a trait has greater concordance in monozygotic twins than in dizygotic twins, the
trait is genetically influenced. Environmental influences will reduce the
concordance in monozygotic twins below 100%.
5.

How are adoption studies used to separate the effects of genes and environment in
the study of human characteristics?
Studies of adoptees, their biological parents, and their adoptive parents separate
environmental and genetic influences on traits. Adoptees share similar
environments with their adoptive parents (because they live in the same house and
eat similar foods), but they share 50% of their genes with each of their biological
parents. If adoptees have greater similarity for a trait with their adoptive parents,
then the trait is environmentally influenced. If the adoptees have greater similarity
for the trait with their biological parents, then the trait is genetically influenced.

*6.

What is genetic counseling?

Genetic counseling provides assistance to clients by interpreting results of genetic
testing and diagnosis; providing information about relevant disease symptoms,
treatment, and progression; assessing and calculating the various genetic risks that
the person or couple faces; and helping clients and family members cope with the
stress of decision-making and facing up to the drastic changes in their lives that
may be precipitated by a genetic condition.

7.

Briefly define newborn screening, heterozygote screening, presymptomatic testing,

and prenatal diagnosis.
Newborn screening: Newborn infants are tested for various treatable genetic
disorders by sampling a few drops of their blood soon after birth.
Heterozygote screening: Normal or asymptomatic individuals in a population
or community are tested for recessive disease alleles to determine the frequency of
the disease allele in the population and to identify carriers, particularly if there is a
relatively high incidence of the disease in the population or community.
Presymptomatic testing: People known to be at higher risk for a disease that
occurs later in life are tested while they are still asymptomatic.
Prenatal diagnosis: Results from prenatal testing for any of a number of genetic
conditions. Techniques such as amniocentesis or chorionic villus sampling are used
to obtain tissue samples of the still developing fetus, or fetal protein or cells in the
maternal circulation are characterized.

*8.

What are the differences between amniocentesis and chorionic villus sampling?
What is the purpose of these two techniques?
Amniocentesis samples the amniotic fluid by inserting a needle into the amniotic
sac, usually performed at about 16 weeks of pregnancy. Chorionic villus sampling
can be performed several weeks earlier (10th or 11th week of pregnancy) and
samples a small piece of the chorion by inserting a catheter through the vagina.
The purpose of these techniques is to obtain fetal cells for prenatal genetic testing.

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9.

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What is preimplantation genetic diagnosis?

Preimplantation genetic diagnosis may be performed on embryos created through
in vitro fertilization. The embryos are cultured until they reach the 8-16 cell stage,
and one cell is removed from each embryo for genetic testing.

APPLICATION QUESTIONS AND PROBLEMS

*10. Joe is color-blind. His mother and father both have normal vision, but his mothers
father (Joes maternal grandfather) is color-blind. All Joes other grandparents have
normal color vision. Joe has three sistersPatty, Betsy, and Lora, all with normal
color vision. Joes oldest sister, Patty, is married to a man with normal color vision;
they have two children, a 9-year-old color-blind boy and a 4-year-old girl with
normal color vision.
(a) Using correct symbols and labels, draw a pedigree of Joes family.

Patty Betsy Joe

Lora

(b) What is the most likely mode of inheritance for color-blindness in Joes family?
X-linked recessive. Only males have the trait, and they inherit the trait from
their mothers, who are carriers. The trait is never passed from father to son.
(c) If Joe marries a woman who has no family history of color-blindness, what is the
probability that their first child will be a color-blind boy?
Barring a new mutation or nondisjunction, zero. Joe cannot pass his color-blind
X chromosome to his son.
(d) If Joe marries a woman who is a carrier of the color-blind allele, what is the
probability that their first child will be a color-blind boy?
The probability is . There is probability that their first child will be a boy,
and there is an independent probability that the first child will inherit the
color-blind X chromosome from the carrier mother. () = .
(e) If Patty and her husband have another child, what is the probability that it will
be a color-blind boy?
Again, . Patty is a carrier because she had a color-blind son. The same
reasoning applies as in part (d). Each child is an independent event.

75 Chapter Six: Pedigree Analysis and Applications

11.

A man with a specific unusual genetic trait marries an unaffected woman and they
have four children. Pedigrees of this family are shown in parts (a) through (e), but
the presence or absence of the trait in the children is not indicated. For each type of
inheritance, indicate how many children of each sex are expected to express the trait
by filling in the appropriate circles and squares. Assume that the trait is rare and
fully penetrant.
(a) Autosomal recessive traitnone

(b) Autosomal dominant trait of each sex

(c) X-linked recessive traitnone

(d) X-linked dominant traitall the female children

(e) Y-linked traitall the male children

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*12. For each of the following pedigrees, give the most likely mode of inheritance,
assuming that the trait is rare. Carefully explain your reasoning.
(a)

Autosomal dominant. Both males and females are affected and can pass on the trait
to both sons and daughters. So the trait must be autosomal and dominant because
affected children are produced in matings between affected and unaffected
individuals. For rare traits, we can assume that unaffected individuals are not
carriers. Therefore, individuals affected with recessive traits marrying unrelated
unaffected individuals would be expected to have all unaffected children.
(b)

X-linked dominant. Superficially this pedigree appears similar to the pedigree in

part (a) in that both males and females are affected, and it appears to be a
dominant trait. However, closer inspection reveals that whereas affected females
can pass on the trait to either sons or daughters, affected males pass on the trait
only to all daughters.

77 Chapter Six: Pedigree Analysis and Applications

(c)

Y-linked. The trait affects only males and is passed from father to son. All sons of an
affected male are affected.
(d)

X-linked recessive or sex-limited autosomal dominant. Because only males show the
trait, the trait could be X-linked recessive, Y-linked, or sex-limited. We can
eliminate Y-linkage because affected males do not pass on the trait to their sons. Xlinked recessive inheritance is consistent with the pattern of unaffected female
carriers producing both affected and unaffected sons and affected males producing
unaffected female carriers, but no affected sons. Sex-linked autosomal dominant
inheritance is also consistent with unaffected heterozygous females producing
affected heterozygous sons, unaffected homozygous recessive sons, and unaffected
heterozygous or homozygous recessive daughters. The two remaining possibilities
of X-linked recessive versus sex-limited autosomal dominant could be distinguished

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if we had enough data to determine whether affected males could have both
affected and unaffected sons, as expected from autosomal dominant inheritance, or
whether affected males can have only unaffected sons, as expected from X-linked
recessive inheritance. Unfortunately, this pedigree shows only two sons from
affected males. In both cases the sons are unaffected, consistent with X-linked
recessive inheritance, but two instances are not enough to conclude that affected
males cannot produce affected sons.
(e)

Autosomal recessive. All the children of the original affected female were carriers.
The first cousins in the consanguineous marriage in the third generation were also
carriers, inheriting the recessive alleles from their carrier parents. The
consanguineous marriage produced two affected children, one boy and one girl,
and four unaffected children.
13.

The trait represented in the following pedigree is expressed only in the males of the
family. Is the trait Y-linked? Why or why not? If you believe the trait is not Ylinked, propose an alternate explanation for its inheritance.

79 Chapter Six: Pedigree Analysis and Applications

Y-linked traits are passed from father to son. This trait cannot be Y-linked because
an affected father can have an unaffected son (indicated by a solid arrow) and also
because we see sons inheriting the trait from their mother (indicated by an open
arrow). Moreover, this trait cannot be X-linked because it is often passed from
father to son, whereas X-linked traits are passed from father to daughter. The most
probable mode of inheritance for this trait is sex-limited (only in males) autosomal
dominant.
*14. A geneticist studies a series of characteristics in monozygotic twins and dizygotic
twins, obtaining the following concordances. For each characteristic, indicate
whether the rates of concordance suggest genetic influences, environmental
influences, or both. Explain your reasoning.
Characteristic
Migraine headaches
Eye color
Measles
Clubfoot
High blood pressure
Handedness
Tuberculosis

Monozygotic
concordance (%)
60
100
90
30
70
70
5

Dizygotic
concordance (%)
30
40
90
10
40
70
5

Migraine headaches appear to be influenced by both genetic and environmental

factors. Markedly greater concordance in monozygotic twins, who share 100%
genetic identity, than in dizygotic twins, who share 50% genetic identity, is
indicative of a genetic influence. However, the fact that monozygotic twins show
only 60% concordance despite sharing 100% genetic identity indicates that
environmental factors also play a role.
Eye color appears to be purely genetically determined because the concordance
is greater in monozygotic twins than in dizygotic twins. Moreover, the monozygotic
twins have 100% concordance for this trait, indicating that environment has no
detectable influence.
Measles appears to have no detectable genetic influence because there is no
difference in concordance between monozygotic and dizygotic twins. Some
environmental influence can be detected because monozygotic twins show less than
100% concordance.
Clubfoot appears to have both genetic and environmental influences, by the
same reasoning as for migraine headaches. A strong environmental influence is
indicated by the high discordance in monozygotic twins.
High blood pressure has both genetic and environmental influences, similar to
clubfoot.
Handedness, like measles, appears to have no genetic influence because the
concordance is the same in monozygotic and dizygotic twins. Environmental
influence is indicated by the less than 100% concordance in monozygotic twins.

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Tuberculosis similarly lacks indication of genetic influence, with the same

degree of concordance in monozygotic and dizygotic twins. The primacy of
environmental influence is indicated by the very low concordance in monozygotic
twins.
15.

In a study of schizophrenia (a mental disorder including disorganization of thought

and withdrawal from reality), researchers looked at the prevalence of the disorder in
the biological and adoptive parents of people who were adopted as children; they
found the following results:
Prevalence of schizophrenia (%)
Adopted persons
Biological parents
Adoptive parents
With schizophrenia
12
2
Without schizophrenia
6
4
(Source: S. S. Kety et al., The biological and adoptive families of adopted individuals who become
schizophrenic: prevalence of mental illness and other characteristics. In The Nature of
Schizophrenia: New Approaches to Research and Treatment, L. C. Wynne, R. L. Cromwell, and S.
Matthysse, Eds. (New York: Wiley, 1978), pp. 2537.)

What can you conclude from these results concerning the role of genetics in
schizophrenia? Explain your reasoning.
These data suggest that schizophrenia has a strong genetic component. The
biological parents of schizophrenic adoptees are far more likely to be schizophrenic
than genetically unrelated individuals (the adoptive parents), despite the fact that
the schizophrenic adoptees share the same environment as the adoptive parents. If
environmental variables (such as chemicals in the water or food or power lines)
were a major factor, then one would expect to see a higher frequency of
schizophrenia in the adoptive parents. Another possibility is that this increased
frequency of schizophrenia in the biological parents simply reflects a greater
likelihood that schizophrenic parents give up their children for adoption. This latter
possibility is ruled out by the data that the biological parents of non-schizophrenic
adoptees do not show a similar increased frequency of schizophrenia compared to
adoptive parents.

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*16. The following pedigree illustrates the inheritance of Nance-Horan syndrome, a
rare genetic condition in which affected persons have cataracts and abnormally
shaped teeth.
I

II

III
1

IV
1

V
1
2
3
4
(Pedigree adapted from D. Stambolian, R. A. Lewis, K. Buetow, A. Bond, and R. Nussbaum.
American Journal of Human Genetics 47(1990):15.)

(a) On the basis of this pedigree, what do you think is the most likely mode of
inheritance for Nance-Horan syndrome?
X-linked recessive. Only males have the condition, and unaffected female
carriers have affected sons.
(b) If couple III-7 and III-8 have another child, what is the probability that the child
will have Nance-Horan syndrome?
The probability is . The female III-7 is a carrier, so there is a probability
that the child will inherit her X chromosome with the Nance-Horan allele and
another probability that the child will be a boy.
(c) If III-2 and III-7 mated, what is the probability that one of their children would
have Nance-Horan syndrome?
The probability is because half the boys will inherit the Nance-Horan allele
from the III-7 carrier female. All the girls will inherit one Nance-Horan allele
from the III-2 affected male, and half of them will get a second Nance-Horan
allele from the III-2 female, so half the girls will also have Nance-Horan
syndrome.

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17.

82

The following pedigree illustrates the inheritance of ringed hair, a condition in

which each hair is differentiated into light and dark zones. What mode or modes of
inheritance are possible for the ringed hair trait in this family?

(Pedigree adapted from L. M. Ashley and R. S. Jacques, Journal of Heredity 41(1950):83.)

This pedigree is consistent with autosomal dominant inheritance. Affected

individuals marrying unaffected individuals have affected children, so the trait is
dominant. Males do not pass the trait to all their daughters, so it cannot be Xlinked dominant.
*18. Ectodactyly is a rare condition in which the fingers are absent and the hand is split.
This condition is usually inherited as an autosomal dominant trait. Ademar FreireMaia reported the appearance of ectodactyly in a family in Sao Paulo, Brazil, whose
pedigree is shown here. Is this pedigree consistent with autosomal dominant inheritance? If not, what mode of inheritance is most likely? Explain your reasoning.

II
1

III

IV
1

(Pedigree adapted from A.Freire-Maia, Journal of Heredity 62(1971):53.)

83 Chapter Six: Pedigree Analysis and Applications

This pedigree shows autosomal recessive inheritance, not autosomal dominant

inheritance. It cant be dominant because unaffected individuals have affected
children. In generation II, two brothers married two sisters, so the members of
generation III in the two families are as closely related as full siblings. A single
recessive allele in one of the members of generation I was inherited by all four
members of generation III. The consanguineous matings in generation III then
produced children homozygous for the recessive ectodactyly allele. X-linkage is
ruled out because the father of female IV-2 is unaffected; he has to be heterozygous.
CHALLENGE QUESTIONS
19.

Draw a pedigree that represents an autosomal dominant trait, sex-limited to males,

and that excludes the possibility that the trait is Y-linked.

This pedigree excludes Y-linkage because not all the sons of an affected male are
affected, an unaffected male has affected sons, and also because it is transmitted
through an unaffected female to her sons.
20.

Androgen insensitivity syndrome is a rare disorder of sexual development, in which

people with an XY karyotype, genetically male, develop external female features.
All persons with androgen insensitivity syndrome are infertile. In the past, some
researchers proposed that androgen insensitivity syndrome is inherited as a sexlimited, autosomal dominant trait. (It is sex-limited because females cannot express
the trait.) Other investigators suggested that this disorder is inherited as a X-linked
recessive trait.
Draw a pedigree that would show conclusively that androgen insensitivity
syndrome is inherited as an X-linked recessive trait and that excludes the possibility
that it is sex-limited, autosomal dominant. If you believe that no pedigree can
conclusively differentiate between the two choices (sex-limited, X-linked recessive
and sex-limited, autosomal dominant), explain why. Remember that all affected
individuals are infertile.
In this case, no pedigree can conclusively differentiate between sex-limited, Xlinked recessive and sex-limited autosomal dominant. In both modes, only males
will exhibit the trait, inherited from their mothers (because males with a single copy
of the allele will be affected and sterile in either case). In both modes, mothers who
have children with the trait will always be heterozygotes because these mothers will

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always have inherited a wild-type allele from their father (who cant have the
androgen insensitivity allele and still be fertile!). Therefore, both modes will exhibit
inheritance of the trait from heterozygous female to heterozygous female, and half
their XY children will have androgen insensitivity and be outwardly female and
sterile.