Unit 1: Laws of Inheritance

Lesson 1.3
Pedigree Analysis
Contents
Introduction 1

Learning Objectives 2

Warm Up 2

Learn about It! 4

Analyzing Inheritance: Peas vs. Humans 4
Using Pedigrees 6
Why Do We Perform Pedigree Analysis? 6
Pedigree Analysis in Genetic Counseling 7
Constructing Pedigrees 7
Analyzing Pedigrees 9
Autosomal Dominant Traits 10
Autosomal Recessive Traits 12

Key Points 22

Check Your Understanding 23

Challenge Yourself 24

Photo Credits 26

Bibliography 26

Key to Try It! 27

Unit 1: Laws of Inheritance

Lesson 1.3

Pedigree Analysis

Introduction
Similar to most of our traits that may or may not compromise our daily survival, such as
having dimples or a hitchhiker’s thumb, many disorders are also genetic in nature. One
example is neurofibromatosis, which is a heritable disorder in humans that affects the skin
and nervous tissues. It occurs in 1 out of 4 000 births. One of its most common symptoms
is the appearance of pea-sized bumps along nerves or under the skin. More severe cases
involve brain and spinal tumors, which result in problems in balance. Since it is a genetic
disorder, neurofibromatosis has no complete cure. However, surgery can be performed to
remove the tumors. Many other genetic disorders occur in the human population. Unlike
the characters of peas that you studied in the previous chapters, human genetic disorders
are not easy to study and understand because of the nature of our reproduction. In this
chapter, you will learn how we can gain an understanding of the inheritance of various
traits that run in human families.

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Learning Objectives DepEd Competency

In this lesson, you should be able to do the This lesson serves as an enrichment for
the following DepEd competency:
following:
● Predict genotypes and
● Understand the importance of phenotypes of parents and

pedigrees in studying inheritance in offspring using the laws of

inheritance
humans.
(STEM_BIO11/12-IIIa-b-1).
● Construct and analyze pedigrees
involving different genetic conditions
in humans.

Warm Up
What’s Up, Doc? 25 minutes
There are cases when a newly born child does not manifest a genetic disorder. Therefore,
many techniques have already been made to determine whether a child or an embryo
during the gestation period possesses a genetic disorder. In this activity, you will look at
some genetic disorders through a simulation of genetic counseling.

Materials
● internet-connected device
● any available relevant props

Procedure
1. Divide the class into four groups.
2. You will be assigned to one of the four genetic disorders listed below. Each disorder
has a designated video that you need to watch.

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a. Cystic fibrosis

What is Cystic Fibrosis?

Demystifying Medicine, “What is Cystic Fibrosis?,” YouTube,
November 24, 2016, shorturl.at/coBC3, last accessed on May
19, 2020.

b. Achondroplasia

Achondroplasia (as seen in "Game of Thrones") - causes,

symptoms, & pathology
Osmosis, “Achondroplasia (as seen in "Game of Thrones") -
causes, symptoms, & pathology,” YouTube, September 26,
2016, shorturl.at/isyS0, last accessed on May 19, 2020.

c. Phenylketonuria

Phenylketonuria - causes, symptoms, diagnosis, treatment,

pathology
Osmosis, “Phenylketonuria - causes, symptoms, diagnosis,
treatment, pathology,” YouTube, October 30, 2019,
shorturl.at/jwO45, last accessed on May 19, 2020.

d. Sickle-cell disease

How this disease changes the shape of your cells - Amber M.

Yates
TED-Ed, “How this disease changes the shape of your cells -
Amber M. Yates,” YouTube, May 19, 2020, shorturl.at/bouVX,
last accessed on May 19, 2020.

Note: Your teacher may provide more genetic disorders depending on the actual
class size. Also, you may be instructed to watch your assigned videos before the
actual meeting.
3. As you watch the video, take note of the important aspects of the disorder, such as
symptoms, patterns of inheritance, and management. Particularly, you must answer
the following questions.

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a. What is its cause? What is its mode of inheritance?

b. What symptoms should be expected?
c. Is there an available treatment? What can be best done?
4. After watching the video, prepare for a three-minute skit.
a. Your presentation should involve a simulation, wherein some members of
your group will act as a group of doctors or genetic counselors.
b. These doctors shall give advice to a couple with an affected child.
c. The storyboard of your skit must contain details about the disorder, possible
coping mechanisms, treatment options, and other information that you deem
necessary.
d. You will be presenting disorders that affect real people. As such, be sensitive
to how your audience will react. Make sure that your skit does not make fun
of anyone afflicted with the conditions.
5. After the presentations, answer the guide questions below.

Guide Questions
1. What are the modes of inheritance of the genetic disorders in the activity?
2. How does it help if a couple determines that an asymptomatic child has a genetic
disorder?
3. What do you think are the challenges in studying the inheritance of genetic disorders
in humans?

Learn about It!

How can you compare the study of inheritance in

peas with that in humans?

Analyzing Inheritance: Peas vs. Humans

Gregor Mendel performed a breakthrough plant breeding experiment that provided us with
a greater understanding of how biological traits are inherited. In his study involving Pisum

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sativum or garden peas, he was able to come up with the laws of inheritance and the
principle of dominance. Relatively, it is easier to study the patterns of inheritance of pea
traits because mating can be controlled. This means assigning the desired characteristics
of the parents in a cross is possible. In addition, the generation time is also relatively
shorter. They can be grown easily and can produce many offspring. A large number of
offspring (i.e., many seeds can be generated in a cross, as in Fig. 1.3.1) that can be obtained
is helpful in performing statistical analysis of inheritance.

Fig. 1.3.1. Studying biological inheritance in peas is relatively easier because of their shorter
generation time and a large number of offspring that can be obtained.

By contrast, studying inheritance in humans (such as the pattern of transmission of albinism

in Fig. 1.3.2) is way more difficult and complicated. Controlled matings are not possible in
humans for obvious ethical reasons. We cannot simply allow two individuals to produce
offspring by virtue of their traits. In addition, the generation time is relatively longer in
humans, and only one or few offspring are produced during every pregnancy, which will
significantly limit the sample size for analysis. Also, current efforts to study inheritance in
humans highly rely on family records, which are oftentimes incomplete.

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Fig. 1.3.2. Human genetics is a relatively more complicated field than plant genetics.

Using Pedigrees
Why Do We Perform Pedigree Analysis?
A useful approach to study the inheritance of traits in humans is pedigree analysis. As
shown in Fig. 1.3.3, a pedigree is a graphical representation of how a trait is inherited
among the members of a family. This is the first effective method introduced to determine
the mode of inheritance of a trait. Given the periodic occurrence of a genetic
characteristic in a family, we can also assess the risk of recurrence, especially if it is a
genetic disorder.

Fig. 1.3.3. Pedigrees are used to determine the chances of a trait recurring in a family.

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However, as mentioned earlier, challenges in studying the inheritance of traits in humans

involve problems in the collection of information. Usually, one can construct an accurate
pedigree of a family from a survey or interview if the interviewee is knowledgeable about
the number of children, sex, and the occurrence of the trait among his or her relatives.
Otherwise, false data can lead to wrong interpretation of a pedigree.

Pedigree Analysis in Genetic Counseling

Genetic counseling is a procedure performed in health institutions (as shown in Fig. 1.3.4),
wherein advice is given to a family afflicted with or at risk of getting a genetic condition. A
genetic counselor usually elaborates on the genetic, psychological, and other implications
of the condition so that the family may adapt as needed. The process of genetic counseling
entails the analysis of pedigrees constructed from a series of questions answered by the
family to generate any pertinent information. However, it will always be critical to accurate
genetic counseling that the family being interviewed has a correct recollection of the
inheritance of traits among their relatives.

Fig. 1.3.4. Genetic health practitioners make a careful analysis of all obtained information to
assess the risk of recurrence of a genetic condition in a family.

Constructing Pedigrees
Symbols and notations are used to construct a pedigree, as shown in Fig. 1.3.5. These
symbols set the standard in all genetic tests or analyses, and they are as follows.
1. Sex. Use squares for male individuals and circles for females.
2. Traits. A shaded square or circle denotes that an individual is affected by the

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condition. Otherwise, the individual does not possess the condition and is
represented by an unshaded shape.
3. Status. A slash is used to denote that an individual is deceased. Not all pedigrees
specify this status of the individuals, however.
4. Proband. Sometimes, pedigrees specify the individual being studied or observed.
Usually, a proband is a member of the family who first sought the attention of a
genetic counselor. A proband is represented by an arrow.
5. Carrier. A half-shade is used to represent that an individual is a carrier for a genetic
condition. Specifically, the carrier individual is said to be heterozygous for the
condition. Take note that the status of being a carrier is not always shown in a
pedigree.
6. Unknown Sex. Sometimes, the family being interviewed prior to genetic counseling
may be certain about the number of children of a relative, but not sure about their
sexes. In such cases, a diamond symbol is used.

Fig. 1.3.5. Symbols and notations used in constructing human pedigrees

7. Mating. Mating between a couple is denoted by a horizontal line connecting them.

8. Offspring. The children of matings are represented by a vertical line that connects
to the parents.

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9. Consanguinity. Mating between genetically related individuals, or a

consanguineous mating, is represented by a double horizontal line.
○ An example of this is when cousins marry each other and have children.
10. Twinning. Twins can be denoted by branching from a common point.
○ Connecting the members of a twin represents a monozygotic or identical
condition. Otherwise, they are considered dizygotic or fraternal.
11. Labels. Roman numerals are used to denote generations. In each generation,
individuals are numbered consecutively from left to right.
○ For example, individual II-2 is an affected son of individuals I-1 and II-2, both
of whom are unaffected.

Analyzing Pedigrees
Identifying whether a trait that runs in the family is dominant or recessive is crucial to the
determination of the chances of recurrence of that trait in the family. This can also
contribute to continuously becoming a more extensive understanding of how human traits
are inherited. It may not be as convenient as generating hundreds of seeds in plant
hybridization. However, it can at least narrow down options regarding the possible mode of
inheritance of a trait in humans.

Remember
In problems involving pedigree analysis, it is rare that the specific
trait or characteristic is provided in the problem. Also, whether an
individual is a carrier or not is not specified. These will somehow
defeat the purpose of the analysis.

For example, we cannot specify that the trait involved is albinism

because you are already familiar with its mode of inheritance, which
is autosomal recessive. Also, the “half-shaded” symbol is not used to
denote the carrier status of an individual. It is the purpose of the
analysis to determine whether an individual is a carrier or not.

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The traits that will be analyzed in this lesson, similar to the characteristics observed by
Mendel in garden peas, are autosomal. The genes for these traits are found in the
autosomes, the set of chromosomes that do not differ between males and females. Other
traits are said to be sex-linked because the genes that code them are found on the sex
chromosomes. These traits will be discussed further in the next chapter of this unit.

The autosomes and sex chromosomes in humans. Recall that human autosomes are the
pairs of chromosomes 1 to 22, and the sex chromosomes represent the 23rd pair. The sex
chromosomes are XX for females and XY for males.

Autosomal Dominant Traits

Compared with recessive traits, dominant traits are relatively easier to identify because
individuals who possess the dominant allele express or manifest the corresponding
phenotype. The pedigree that is given in Fig. 1.3.6 represents the inheritance of a trait that
follows the autosomal dominant mode of inheritance.
1. Note that in this mode of inheritance, an affected individual shall have at least
one affected parent.
a. In the given pedigree, both II-2 and II-4 inherit their dominant alleles from
their father, I-1.
b. The same is true for individual III-2, who inherited a dominant allele from his
mother, II-2.

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2. Given the previous case, autosomal dominant traits have the tendency to not skip
generations. This means that the trait may most likely be present in every
generation.
3. We can also determine the genotypes of the individuals in the given pedigree.
a. Suppose that I-1 is heterozygous Aa, and I-2 is aa. As a result, aa individuals
are present in the offspring (i.e., II-3, II-6, and II-7).
b. Thus, II-2 and II-4 must be heterozygous, Aa.

Fig. 1.3.6. A sample pedigree for the inheritance of an autosomal dominant trait that runs in
the family shows that an affected offspring should have at least one affected parent.

Examples of autosomal dominant traits

include achondroplasia, a form of
dwarfism. Due to a dominant mutation
in a gene that codes for the normal
development of bones, an affected
individual ends up having short
stature. Particularly, these individuals
suffer from the impairment of the
conversion of cartilage into bones
during development. As shown in Fig.
1.3.7, one notable individual with
achondroplasia is Peter Dinklage.

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Autosomal Recessive Traits

In an actual analysis of pedigrees during genetic health consultations, identifying autosomal
recessive traits are relatively more challenging. The difficulty in detecting them lies on the
premise that an affected child usually has two unaffected parents. In such cases, both
parents must be carriers of the recessive allele. Furthermore, recessive traits that are
rare in populations usually appear when members of a couple are genetically related to
each other; hence, a consanguineous mating.

Fig. 1.3.8. A sample pedigree for the inheritance of an autosomal recessive trait that runs in
the family shows that an affected person may have two unaffected parents.

1. The given pedigree in Fig. 1.3.8 shows an autosomal recessive trait because
individual II-2, who is affected, has two unaffected parents, I-1 and I-2.
2. The same is true for individual III-3, who is also affected but has two unaffected
parents.
3. Given the pedigree, we can also conclude some genotypes.
a. Given that individual II-2 is affected (aa), both of the unaffected parents must
be heterozygous, Aa. In addition, individual II-4 can be concluded as
heterozygous given that she has an affected child. II-1 can either be
homozygous or heterozygous dominant.

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b. Likewise, the affected individual III-3 must have a genotype of aa. Both of her
parents must be heterozygous, Aa. This includes II-4.

Cystic fibrosis is an autosomal recessive genetic condition that results from the mutation of
a gene that codes for the synthesis of chloride ion channels in cell membranes. These
channels are important to create freely flowing mucus. Thus, one of its most serious
consequences is the continuous buildup of mucus in respiratory and digestive organs.
This buildup clogs the airways and ducts in our bodies. Other symptoms of cystic fibrosis are
shown in Fig. 1.3.9.

Fig. 1.3.9. Consequences of having two mutated alleles for cystic fibrosis

Another autosomal recessive condition in humans is the sickle cell disease. This disease
resulted from the mutation of the hemoglobin gene. As previously discussed, hemoglobin
is an important respiratory pigment that enables our red blood cells to transport oxygen.
This mutation which produces malformed hemoglobin, also results in an alteration in the
shape of the erythrocytes, hence the name sickle cell disease. As shown in Fig. 1.3.10,
affected individuals have sickle-shaped (or crescent-shaped) erythrocytes that taper on both

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ends. Unlike the normal ones, sickle-shaped red blood cells die prematurely. Also, these
abnormal blood cells can become stuck in blood vessels, which may lead to other
complications. Like phenylketonuria (discussed in an earlier chapter) and cystic fibrosis, two
copies of the mutant recessive alleles are required to have sickle cell disease.

Fig. 1.3.10. Sickle-shaped red blood cells have an impaired capacity for gas transport.

Did You Know?

Individuals who have one copy of the mutant allele for sickle cell
disease have a normal phenotype. These heterozygous individuals
were found to have increased resistance against malarial
infection.

In areas with a high prevalence of malarial infection, such as in

Africa, carriers of the gene for sickle cell disease are less prone to
acquire malaria. Apparently, having some sickle-shaped red blood
cells interferes with the infection process of Plasmodium, the
malarial parasite.

How does consanguineous mating become

disadvantageous to the members of the couple
involved?

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Remember
When analyzing pedigrees, and you are asked to provide the
genotypes of the individuals, there may be cases when you can
leave the second allele blank.

For example, an individual has a dominant phenotype, A__.

However, due to insufficient information, one cannot determine
whether the second allele is dominant or recessive. Thus, you may
leave it as it is.

Let’s Practice!

Example 1
A trait that runs in the family given below was analyzed by a genetic counselor. She was able
to illustrate its transmission through the pedigree given below. What is the mode of
inheritance of this trait? Justify your answer. (Take note that the carriers, if there are any, are
not marked with dots)

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Solution
Step 1: You are asked to determine the mode of inheritance of the trait.

Step 2: The pedigree for the trait that runs in the family is given.

Step 3: Assuming that the trait is autosomal dominant, then we can assign the
genotypes shown in the figure below.
A__ : affected individual
aa : unaffected individual

Individual III-3 is not possible because having an offspring with a dominant

trait is not applicable if both parents are recessive for the trait.

Step 3: Assuming that the trait is autosomal recessive, then we can assign the
genotypes shown in the figure below.
A__ : unaffected individual
aa : affected individual

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Step 5: Find the answer.

The trait in the given pedigree follows an autosomal recessive mode of inheritance
because two unaffected parents had an affected child.

1 Try It!
Jane and Robert married, and they had three children. If a genetic disorder, which
neither of them possesses, appeared in their third child, what is the mode of
inheritance of the condition?

Example 2
The following pedigree below shows the inheritance of an autosomal dominant trait in a
family. Given this mode of inheritance, what are the genotypes of all the individuals in
the pedigree? (Take note that the carriers, if there are any, are not marked with dots.)

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Unit 1: Laws of Inheritance

Solution
Step 1: You are asked to provide the genotypes of all the individuals in the given
pedigree.

Step 2: A pedigree that involves an autosomal dominant trait is given.

Step 3: Assign the corresponding genotypes.

A__ : affected individual
aa : unaffected individual

Step 4: Determine the genotypes of the individuals based on their phenotypes.

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Step 5: Find the answer.

Individuals I-1, I-3, II-2, II-4, II-5, and III-2 have the genotype Aa. Individuals I-2, I-4, II-1, II-3,
II-6, III-1, and III-3 have the genotype aa.

2 Try It!
Analyze the following pedigree below. Determine the mode of inheritance of the trait
that runs in the given family. Take note, however, that you have no information on
who among the family members is a carrier.

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Example 3
Agnes and Jerwin married. Their first child is a girl named Dorothy. She has two brothers
named Mark and Raymond, respectively. Mark and Raymond have a genetic condition that
causes them to have dark urine, which neither of their parents has. Later on, Dorothy
married Michael, who is unaffected, and they had three children. The first two children, a
boy, and a girl, respectively, are normal. However, their third child, who is a boy, has the
genetic condition that Mark and Raymond have. Furthermore, Raymond married Melissa,
who is unaffected. They have three children, the first two being boys, and the third one is a
girl, all of whom are affected. Construct a pedigree for this family and determine the mode
of inheritance of the genetic condition.

Solution
Step 1: Draw a pedigree for the given family with respect to the formation of dark
urine. Also, the mode of inheritance of this trait must be determined.

Step 2: We can tabulate the individuals in the problem to organize the given.

Generation 1 Generation 2 Generation 3

Son 1: unaffected
Dorothy: unaffected
Daughter 1: unaffected
Michael: unaffected
Son 2: affected
Agnes: unaffected
Mark: affected
Jerwin: unaffected
Son 1: affected
Raymond: affected
Son 2: affected
Melissa: unaffected
Daughter 1: affected

Step 3: Draw the pedigree.

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Step 4: Determine the mode of inheritance.

The mode of inheritance must be autosomal recessive. Agnes and Jerwin are
both unaffected, and they had two affected sons. Likewise, Dorothy and his
husband are both unaffected, but they had one affected son. Their unaffected
children (son 1 and daughter 1) can be homozygous dominant or
heterozygous.

Step 5: Find the answer.

The mode of inheritance must be autosomal recessive.

3 Try It!
Jane married Paul, who has a certain genetic condition that runs in his family. They
had three children. Their first child, a boy named Marco, does not have the condition.
However, their second and third children, Rica and Angela, both have the condition.
Later on, Angela married Dexter. They have five children, the first child being a girl
named Roxi. The rest are boys, the last two being affected by the condition.
Construct a pedigree of their family and analyze the mode of inheritance of the trait.

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Did You Know?

The OMIM or Online Mendelian Inheritance in Man is an
extensive online database about human genes and genetic
phenotypes. It contains comprehensive information of all known
Mendelian genetic disorders, comprising about 15 000 genes. This
is a free-access site, the link to which is provided below.

Online Mendelian Inheritance in Man.

John Hopkins University, “OMIM ®, Online Mendelian
Inheritance in Man ®, Online Catalog of Human Genes
and Genetic Disorders, Last updated on May 18, 2020,
https://www.omim.org/, last accessed on May 20, 2020.

Key Points
_________________________________________________________________________________________
● The analysis of the inheritance of traits in humans is a far more complicated task
compared with that of peas and fruit flies.
● The challenge of analyzing human inheritance lies in their longer generation time, the
limited sample size for analysis, and the impossibility of performing matings in
controlled environments.
● Pedigree analysis was devised to observe and analyze how a trait runs in families. It
uses a pedigree, a pictorial representation of the transmission of a characteristic in at
least two generations of families.
● Pedigrees in basic research and genetic counseling use a set of standard symbols and
notations.
● Pedigrees are used to determine the mode of inheritance of a trait.
○ Individuals with an autosomal dominant trait usually have at least one affected
parent.

○ Individuals with an autosomal recessive trait usually have no affected parents.

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Although, still, there are cases when one parent is also affected by the recessive
condition.
● Different genetic conditions in humans are autosomal. Achondroplasia is inherited as a
dominant trait, while phenylketonuria, cystic fibrosis, and sickle cell disease are
inherited as recessive traits.

The uses and applications of pedigree analysis in studying human inheritance

__________________________________________________________________________________________

Check Your Understanding

A. Determine the accuracy of each of the following statements.

Write true if the statement is correct and false if otherwise.

1. Controlled matings are possible in humans.

2. Generation time is shorter in peas than in humans.
3. Pedigree analysis can help assess the risk of recurrence of a genetic disorder.
4. Pedigrees are useful because of the very large sampling size possible for human
matings.
5. A proband is an individual who first sought the attention of a genetic counselor.
6. A couple whose members are second-degree cousins is an example of
consanguinity.
7. Cystic fibrosis is autosomal dominant.
8. Sickle cell disease is autosomal recessive.
9. A trait is autosomal recessive if two copies of the allele are needed to manifest the
trait.

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10. A trait is autosomal dominant if an affected individual has two unaffected parents.

B. By using gene B, determine the genotypes of the individuals in the

given pedigree below.

1. I-1 ___ 6. III-1 ___

2. I-2 ___ 7. III-3 ___
3. II-2 ___ 8. III-4 ___
4. II-3 ___ 9. III-5 ___
5. II-5 ___ 10. III-6 ___

Challenge Yourself

Answer the following questions.

1. Why is analyzing the inheritance of biological traits in humans more challenging than
that in fruit flies and peas?
2. Why is the mating between biological cousins genetically risky?
3. What are the limitations of performing pedigree analyses?
4. Determine the mode of inheritance of the trait that runs in the given pedigree below.
Justify your answer.

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5. Determine the mode of inheritance of the trait that runs in the given pedigree below.
Justify your answer.

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Photo Credits
Vanuatu-humans-of-vanuatu-2 by Graham Crumb/Imagicity.com is licensed under CC BY-SA
3.0 via Wikimedia Commons.

Eye Care Consultation by National Eye Institute is licensed under CC BY 2.0 via Flickr.

Peter Dinklage (9350750232), cropped, by Gage Skidmore from Peoria, AZ, United States of
America is licensed under CC BY-SA 2.0 via Wikimedia Commons.

Bibliography
Brooker, J. Concepts of Genetics (1st ed.). New York, USA: McGraw-Hill Companies Inc., 2012.

Klug, W.S, and Cummings, M.R. Concepts of genetics (6th ed). Upper Saddle River, N.J:
Prentice-Hall. 2003.

Pierce, B. Genetics: a conceptual approach (8th ed). New York: W.H. Freeman. 2012.

Reece J., Taylor M., Simon E., and Dickey J. Campbell Biology: Concepts and Connections (7th
ed.). Boston: Benjamin Cummings/Pearson. 2011.

Snustad, D.P., and Simmons, M.J. Principles of Genetics (6th ed.). Hoboken, NJ: Wiley. 2012.

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Key to Try It!

1. The trait is autosomal recessive because neither of the parents has the trait, but it
was able to appear in one of the offspring.
2. Autosomal dominance is possible in the given pedigree. This can be seen in the
photo below.
Autosomal dominant

3. The pedigree for the inheritance of this trait can be illustrated as follows. Both
autosomal dominant and autosomal recessive modes are possible. Thus, more data
is needed to determine the actual mode of inheritance.

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