Primer in Genetics and Genomics

Biological Research for Nursing

1-8
Primer in Genetics and Genomics, ª The Author(s) 2017
Reprints and permission:
[Link]/[Link]
Article 4—Inheritance Patterns DOI: 10.1177/1099800417708616
[Link]/home/brn

Lisa B. Aiello, RN, MSN, AOCNS1 and

Beth Desaretz Chiatti, PhD, RN, CTN, CSN1

Abstract
Since the completion of the Human Genome Project, much has been uncovered about inheritance of various illnesses and
disorders. There are two main types of inheritance: Mendelian and non-Mendelian. Mendelian inheritance includes autosomal
dominant, autosomal recessive, X-linked, and Y-linked inheritance. Non-Mendelian inheritance includes mitochondrial and
multifactorial inheritance. Nurses must understand the types of inheritance in order to identify red flags that may indicate the
possibility of a hereditary disorder in a patient or family.

Keywords
genotype, phenotype, allele, Mendelian inheritance, dominant, recessive, homozygous, heterozygous, Punnett square, mitochon-
drial inheritance, pedigree, non-Mendelian inheritance, multifactorial inheritance

The Human Genome Project (HGP) was an international Coleman et al., 2014). Thus, in order to integrate genetics and
research initiative that began in 1990 and was completed in genomics into their practice, nurses must have a basic under-
2003 with the successful sequencing of the entire human gen- standing of inheritance patterns. In this article, we discuss the
ome (National Human Genome Research Institute [NHGRI], basic concepts of inheritance, Mendelian and non-Mendelian
2012). The HGP identified the approximately 20,500 genes in inheritance, probabilities of inheritance, construction of a
each human (the complete set of human genes) as well as their three-generation pedigree, and identification of red flags that
locations. Finally, the project identified the blueprint for human indicate the need for a referral to a genetics specialist. Addi-
health (NHGRI, 2012). Further information about the HGP can tional genetic and genomic educational resources for nurses are
be found at [Link] Subsequent research has available in both print and electronic form (Tonkin, Calzone,
suggested that the focus of genetics (the study of single-gene Jenkins, Lea, & Prows, 2011; see resources in Table 1).
disorders) should expand to include genomics, the study of how
genes interact with each other and with environmental, psycho-
social-behavioral, and cultural factors. Genetics and genomics What Is Inheritance?
provide the basis for health, illness, disease risk, and treatment Each human nucleated cell contains 46 chromosomes arranged
response (Clark, Adamian, & Taylor, 2013). Genetics and in 23 pairs. There are 22 pairs of autosomes and 1 pair of
genomics have already moved into mainstream health care. allosomes or sex chromosomes (XX or XY). An individual
Presently, research in the field of genetics and genomics is inherits one chromosome of each pair from each parent. The
focused on personalized medicine and precision medicine with chromosomal complement of a normal female is 46, XX, while
the hope of improving health outcomes by developing custo-
mized therapies for individual patients.
1
Since knowledge in genetics and genomics is ever increas- College of Nursing and Health Professions, Drexel University, Philadelphia,
ing, it is important for nurses to integrate genetics and geno- PA, USA
mics into their practice, regardless of academic preparation,
Corresponding Author:
role, practice setting, or clinical specialty (Consensus Panel Lisa B. Aiello, RN, MSN, AOCNS, College of Nursing and Health Professions,
on Genetic/Genomic Nursing Competencies, 2009). This pro- Drexel University, 136 E. Hartwell Lane, Philadelphia, PA 19118, USA.
cess includes obtaining a complete family medical history, Email: lba34@[Link]
constructing a minimum of a three-generation pedigree, iden-
tifying “red flags” that may indicate the possibility of a heredi- Series Information:
The “Primer in Genetics and Genomics” series is a collaboration between
tary syndrome or risk of disease, providing patient education, Biological Research for Nursing and the International Society of Nurses in
and referring the patient or family to a genetic specialist for a Genetics (ISONG). Sheila A. Alexander, PhD, RN, FCCM, serves as guest
comprehensive evaluation, as indicated (Calzone et al., 2016; editor for the series.
2 Biological Research for Nursing XX(X)

Table 1. List of Resources on Genetics and Genomics for Health the observable ways in which that DNA sequence manifests in
Professionals. the individual, such as eye color, hair color, or susceptibility to
Resource Name Resource Website
a disease (Beery & Workman, 2012). An allele is an alternate
form of a gene. For example, in the case of eye color, there is a
American Medical Association, [Link] gene responsible for the amount and quality of melanin. Differ-
“Collecting a Family History” delivering-care/collecting- ent versions of this gene (i.e., different alleles) may lead to more
family-history or less melanin in the eye, thus affecting eye color (National
Cincinnati Children’s Genetic https://
Institute of Health, n.d.). There can be many different alleles for
Education Program [Link]/
education/clinical/nursing/ each gene. An allele in its most common form in a population is
genetics referred to as wild type. A mutation is an allele that has a per-
Consensus Panel on Genetic/ [Link] manent alteration in its DNA sequence (Kenner & Lewis, 2013).
Genomic Nursing careers/ Mutations can be inherited or sporadic (not inherited). They can
Competencies (2009) healthprofessionaleducation/ be disease causing or represent a normal variation. A polymorph-
[Link] ism is a normal variation that does not have a deleterious effect.
DNA Learning Center [Link]
When an individual has two identical alleles for a particular
GENE Tests International [Link]
Genetics Clinic Directory gene, it is termed homozygous; when an individual has two
Genetic Alliance [Link] different alleles for a gene, it is termed heterozygous.
Genetics Home Reference [Link] Patterns of inheritance vary. The main types of genetic
Genetics in Primary Care https:// inheritance include traditional Mendelian inheritance and
Institute: A tool kit to improve [Link]/ nontraditional, or non-Mendelian, inheritance (Kenner &
care for pediatric patients with Documents/GPCI_Toolkit.pdf Lewis, 2013).
genetic conditions in primary
care
International Society of Nurses in [Link] Mendelian Inheritance
Genetics
Jackson Laboratory (formerly, the [Link] Mendelian inheritance is named after the Austrian monk and
National Coalition for Health and-learning/clinical-and- scientist Gregor Mendel who experimented with crossbreeding
Professional Education in continuing-education pea plants in the mid-19th century (refer to the first article in
Genetics) the Primer in Genetics and Genomics series for more informa-
[Link] [Link]
tion about Gregor Mendel; Dorman, Schmella, & Wesmiller,
March of Dimes, “Your Family [Link]
Health History” pregnancy/your-family-health- 2017). Mendel coined the terms dominant and recessive to
[Link] explain the relationship between two versions of a gene (Lea-
National Cancer Institute Cancer [Link] vitt, 2010). He identified the appearance of parental genes in
Genetics Services Directory cancer/causes-prevention/ offspring as dominant or recessive traits: If a pea plant was
genetics/directory heterozygous for a gene, the gene would express the dominant
National Human Genome [Link] allele, thus masking the recessive allele (National Institutes of
Research Institute: Education education/
Health, National Human Genome Research Institute, n.d.).
Talking Glossary of Genetic [Link]
Terms glossary/ Today, our knowledge has increased to understand that an
All About the Human Genome [Link] allele does not have to be dominant or recessive. Rather, if two
Project 10001772/all-about-the– alleles of a gene are present, both can be expressed.
human-genome-project-hgp/ In a single-gene disorder, the individual inherits a single
Fact Sheets on Science, Research, [Link] affected allele (the gene is mutated) or a pair of affected alleles
Ethics, and the Institute 10000202/fact-sheets/ (both copies of the gene are mutated). If the affected allele is on
Online Genetics Education [Link]
a nonsex chromosome, the disorder is referred to as an auto-
Resources 10000464/onlinegenetics-
education-resources/ somal disorder, and if the affected allele is on a sex chromo-
National Human Genome [Link] some, it is referred to as an X-linked or Y-linked disorder
Research Institute Project (Kenner & Lewis, 2013). Common Mendelian inheritance pat-
National Society of Genetic [Link] terns include autosomal dominant, autosomal recessive,
Counselors: About Genetic X-linked recessive, X-linked dominant, and Y-linked.
Counselors
Find a Genetic Counselor [Link]
Autosomal dominant inheritance. In an autosomal dominant dis-
(directory) gc-search
order, only one copy of the affected (dominant) allele is
required for the person to have the disorder or disease. An
individual has a 50% chance of inheriting the affected allele
the chromosomal complement of a normal male is 46, XY. from an affected parent. Males and females are equally at risk.
Genotype refers to an individual’s actual DNA sequence at a Conversely, an affected individual with one mutated allele has
specific locus (location on a chromosome), and phenotype is a 50% chance of passing the mutated allele on to future
Aiello and Chiatti 3

Figure 1. Autosomal dominant inheritance. Source. Illustration:

Figure 2. Autosomal recessive inheritance. Source. Illustration:
National Library of Medicine (United States). Genetics Home
National Library of Medicine (United States). Genetics Home
Reference [Internet]. Bethesda (MD): The Library; April 11, 2017.
Reference [Internet]. Bethesda (MD): The Library; April 11, 2017.
[Illustration] Autosomal dominant; (cited April 13, 2017); (about one
[Illustration] Autosomal recessive; (cited April 13, 2017); (about one
screen). Available from [Link]
screen). Available from [Link]
inheritancepatterns
inheritancepatterns

offspring (see Figure 1). Over half of the 6,000 classified Men- with SCT may experience complications and/or symptoms
delian disorders are autosomal dominant (Kenner & Lewis, (Centers for Disease Control and Prevention, 2016). When both
2013). Some examples of disorders that are transmitted in an parents are carriers of an autosomal recessive disorder, each
autosomal-dominant pattern include achondroplasia (caused by child has a one-in-four chance (25%) of inheriting the disorder,
one mutated allele in the FGFR3 gene), Huntington’s disease a 50% chance of inheriting one copy of the affected gene and
(caused by one mutated allele in the HTT gene), neurofibroma- being a carrier, and a 25% chance of not inheriting the affected
tosis Type 1 (caused by one mutated allele in the NF1 gene), gene at all. Males and females are equally at risk (see Figure 2).
neurofibromatosis Type 2 (caused by one mutated allele in the If one parent is homozygous for an autosomal recessive dis-
NF2 gene), Marfan syndrome (caused by one mutated allele in order (has two copies of the affected gene and thus has the
the FBN1 gene), and polycystic kidney disease (caused by one disorder) and the other parent is not a carrier and does not have
mutated allele in either the PKD1 or PKD2 gene; National the disorder (does not have an affected gene), each of their
Institute of Health, n.d.). children has a 100% chance of being a carrier and a 0% chance
of exhibiting the recessive disorder (affected; Kenner & Lewis,
2013). Examples of autosomal recessive disorders include cys-
Autosomal recessive inheritance. Both copies of the affected
tic fibrosis (caused by two mutated copies of the CFTR gene),
(recessive) allele are required for a person to have an autosomal
sickle cell disease (caused by two mutated copies of the HBB
recessive disorder or disease. The affected offspring thus inher-
gene), phenylketonuria (caused by two mutated copies of the
its two copies of the affected allele, one from each carrier
PAH gene), and Tay–Sachs disease (caused by two mutated
parent. Individuals who inherit only one copy are carriers of
copies of the HEXA gene; National Institute of Health, n.d.).
the disorder but do not have the clinical manifestations of the
disease. However, there are some exceptions to this rule. For
example, if a person has only one copy of a mutation on the X-linked inheritance. X-linked disorders are due to mutations on
HBB gene (only one allele is affected), the person has sickle- the X chromosome. These mutations can be inherited from the
cell trait (SCT), not sickle cell disease. Usually, a person with mother (XX) or the father (XY). X-linked disorders can also be
SCT does not have any symptoms, but in rare cases, people dominant or recessive.
4 Biological Research for Nursing XX(X)

Figure 3. X-linked recessive inheritance. Source. Illustration: National Library of Medicine (United States). Genetics Home Reference [Internet].
Bethesda (MD): The Library; April 11, 2017. [Illustration] X-linked recessive; (cited April 13, 2017); (about 1 screen). Available from https://
[Link]/primer/inheritance/inheritancepatterns

For an X-linked recessive disorder to occur in females, the chance that each daughter will have the disorder and a 0%
affected individual must have two copies of the affected gene, chance that he would pass on the disorder to any son
one in each of her X chromosomes. However, if a male’s single (see Figure 4). X-linked dominant disorders include fragile X
X chromosome has an affected gene, leaving the individual syndrome, Charcot–Marie–Tooth disease, hereditary hypopho-
with no healthy copy of the X chromosome, the male will have sphatemia rickets, and Rett syndrome (National Institutes of
the disorder. Males only inherit X-linked recessive disorders Health, n.d.).
from a mother who is either a carrier or affected since they
inherit the Y chromosome from the father. Most X-linked dis- Y-linked inheritance. Y-linked disorders are due to mutations on
orders are recessive. If a female is a carrier of an X-linked the Y chromosome; therefore, these disorders only occur in
recessive disorder, there is a 50% chance that each son will males and are transmitted from father to son (see Figure 5).
have the disorder (affected) and a 50% chance that each daugh- Y-linked genes are important in male sexual development and
ter will be a carrier. If a male is affected with an X-linked spermatogenesis. Y-linked disorders include Y-chromosome
recessive disorder (which he had to have inherited from his infertility and some cases of Swyer syndrome (National
mother), there is a 100% chance that each of his daughters will Institutes of Health, n.d.). Y-linked disorders have also been
be at least a carrier. The daughters can only be affected with the associated with skin abnormalities, hairy ears, webbed toes,
recessive illness if they also inherit an affected allele from their height determination, and tooth enamel abnormalities (Kenner
mother. The male affected with an X-linked recessive disorder & Lewis, 2013).
has a 0% chance of passing the disorder on to a son. As men-
tioned above, a son can only inherit an X-linked recessive Punnett squares. Punnett squares are a useful tool for evaluating
disorder from his mother (Kenner & Lewis, 2013; see Figure 3). the probability that an offspring will inherit a disorder via
Some examples of X-linked recessive disorders include Duchenne Mendelian inheritance mechanisms. It is important to note that
muscular dystrophy, Fabry disease, hemophilia, red–green color a Punnett square determines probability rather than absolute
blindness, and Lesch–Nyhan syndrome (National Institutes of certainty since there are other genetic and environmental fac-
Health, n.d.). tors that influence single-gene expression. Nonetheless, this
X-linked dominant disorders are rare, severe, and usually tool can assist in determining risk for disease and help with
lethal. If a female has an X-linked dominant disorder, there is a reproductive decision-making. A Punnett square is drawn as a
50% chance that each son will have the disorder and a 50% two-by-two grid. The dominant allele from either parent is
chance that each daughter will have the disorder. If a male is represented by an upper case letter and the recessive allele by
affected with an X-linked dominant disorder, there is a 100% a lower case letter. Two upper case letters represent a
Aiello and Chiatti 5

Figure 4. X-linked dominant inheritance. Source. Illustration: National Library of Medicine (United States). Genetics Home Reference [Inter-
net]. Bethesda (MD): The Library; April 11, 2017. [Illustration] X-linked dominant; (cited April 13, 2017); (about 1 screen). Available from
[Link]

homozygous dominant trait or disorder, and two lower case combined with lifestyle and/or environmental factors that
letters represent a homozygous recessive trait or disorder. The increase the risk. For example, an individual may have a pre-
resulting diagram allows for the prediction of the probability disposition to diabetes mellitus. If this individual is healthy,
(expressed as a percentage) of an offspring inheriting a Men- with an ideal body weight, and eats a healthy diet of fruits and
delian disorder (see Figures 6 and 7). vegetables, avoiding fast food and sugary food, she or he may
It is important to remember that the probability of inheri- never develop diabetes. Some examples of complex disorders
tance of a Mendelian disorder is the same for each offspring of include diabetes mellitus, epilepsy, glaucoma, hypertension,
the same parents. Inheritance results of one offspring do not ischemic heart disease, manic depression, and schizophrenia.
affect the probabilities of another offspring. Accordingly, if
one offspring has a 50% chance of inheriting a dominant allele, Mitochondrial inheritance. Mitochondrial inheritance occurs
each subsequent offspring has a 50% chance of inheriting the through DNA found in the mitochondria of cells. Mitochon-
same dominant allele. The Punnett square thus reflects the drial DNA is present in the egg cell at the time of conception;
probabilities for each offspring. therefore, a person’s mitochondrial DNA is inherited from the
mother (Center for Genetics Education, 2015). Mitochondrial
DNA differs from chromosomal DNA and contains 37 genes
Non-Mendelian Inheritance (National Institutes of Health, n.d.). These genes are responsi-
ble for mitochondrial function. Leber hereditary optic neuro-
Additional patterns of inheritance, other than those described pathy is an example of a mitochondrial disorder.
by Mendel, include complex, or multifactorial, inheritance and
mitochondrial inheritance.
Visualizing Inheritance Patterns
Complex inheritance. While Mendelian inheritance involves a
single gene, complex, or multifactorial, inheritance describes
via Pedigrees
the process by which multiple genes in combination with life- In Essentials of Genetic and Genomic Nursing: Competencies,
style and/or environmental factors cause a trait or disorder. Curricula Guidelines, and Outcome Indicators, the Consensus
Researchers and clinicians thus understand less about the pos- Panel on Genetic/Genomic Nursing Competencies (2009)
sible causes of complex disorders than they do about Mende- states that all nurses, regardless of academic preparation or
lian disorders. Complex disorders are usually due to mutations practice setting, must possess the ability to provide competent
in multiple genes that cause a predisposition to the disorder genetic and genomic-based nursing care, which includes the
6 Biological Research for Nursing XX(X)

A a
A AA Aa

a Aa aa

Figure 7. Punnett square illustrating the case of both parents being

carriers of an autosomal recessive disease. A ¼ autosomal dominant
allele; a ¼ autosomal recessive allele. Each offspring has a 25% chance
(one of the four) of having the autosomal recessive disease, a 50%
chance (two of the four) of being a carrier, and a 25% chance (one of
the four) of not being a carrier and not having the disease.

Figure 5. Y-linked inheritance. Source. Illustration: National Library of

Medicine (United States). Genetics Home Reference [Internet]. Figure 8. Example of a pedigree. This image, obtained from the
Bethesda (MD): The Library; April 11, 2017. [Illustration] Y-linked; Creative Commons, was downloaded from Wikipedia Commons on
(cited April 13, 2017); (about 1 screen). Available from https:// December 18, 2016. Author: Yassine Mrabet. [Link]
[Link]/primer/inheritance/inheritancepatterns [Link]/wiki/File:[Link]

family and to identify inheritance patterns. Figure 9 illustrates

A a the standard nomenclature clinicians use to construct a pedi-
a Aa aa gree (Bennett, French, Resta, & Doyle, 2008). A pedigree
should include all family members, including both maternal
a Aa aa and paternal lineages; a minimum of three generations;
illnesses of each family member; current age, age at diagnosis
of an illness, and age at death; miscarriages or stillbirths; adop-
Figure 6. Punnett square illustrating the case of one parent with an
autosomal dominant disease. A ¼ autosomal dominant allele; a ¼
tions; ethnicity; birth defects; intellectual development disor-
autosomal recessive allele. Each offspring has a 50% chance (two of ders; and known genetic conditions (Genetics in Primary Care
the four) of inheriting an autosomal dominant disorder and a 50% Institute, n.d.a). Specific features of Mendelian inheritance
chance of not inheriting it. may be visualized on a pedigree. For instance, autosomal domi-
nant disorders carry a 50% chance of inheritance, affect males
ability to elicit a minimum of a three-generation family history, and females equally, and do not skip a generation (see, e.g.,
construct a minimum of a three-generation pedigree, identify Figure 10). Autosomal recessive disorders carry a 25% risk of
red flags within the family history, and, when needed, refer inheritance, affect males and females equally, and appear to
patients to the appropriate genetics professional, such as a skip a generation (see, e.g., Figure 11). These disorders do not
geneticist (MD), genetics counselor, or nurse credentialed actually skip a generation; however, there may be a generation
as a genetics nurse (Advanced Genetics Nurse-Board in which individuals are carriers only and not affected with the
Certified). illness. X-linked disorders affect all males and 50% of females.
Y-linked disorders affect only males and all male offspring.

Pedigree
A pedigree is a pictorial representation of a family medical
Red Flags
history (see, e.g., Figure 8). The purpose of a pedigree is to Specific red flags in a family’s history may indicate the pres-
be able to visualize whether a disease is tracking through a ence of a hereditary disorder. These red flags are easiest to
Aiello and Chiatti 7

Figure 9. Standard pedigree nomenclature. This image was obtained from [Link] and is
available under the GNU Free Documentation License 1.3.

Affected (circle = female, square = male)

Unaffected

Carrier

Figure 10. Pedigree chart showing the inheritance pattern of an

autosomal dominant disorder. This image was obtained from the
Creative Commons and downloaded from Wikimedia Commons on Figure 11. Pedigree chart showing the inheritance pattern of an
December 18, 2016. Author: Simon Caulton. [Link] autosomal recessive disorder.
[Link]/wiki/File:Autosomal_dominant.png
8 Biological Research for Nursing XX(X)

visualize once a pedigree is constructed. The Genetics in Pri- References

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Summary Dorman, J. S., Schmella, M. J., & Wesmiller, S. W. (2017). Primer in
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Authors’ Contribution Upper Saddle River, NJ: Pearson.
Lisa B. Aiello contributed to conception, design, acquisition, analysis, Leavitt, S. A. (2010). Gregor Mendel: The father of modern genetics.
and interpretation; drafted the manuscript; critically revised the manu- In Deciphering the genetic code: Marshall Nirenberg. Retrieved
script; gave final approval; and agrees to be accountable for all aspects from [Link]
of work ensuring integrity and accuracy. Beth Desaretz Chiatti con- National Human Genome Research Institute. (2012). An overview of
tributed to conception, design, acquisition, analysis, and interpreta- the Human Genome Project. Retrieved from [Link]
tion; drafted the manuscript; gave final approval; and agrees to be
.gov/12011238
accountable for all aspects of work ensuring integrity and accuracy.
National Institutes of Health. (n.d.). Genetics home reference.
Declaration of Conflicting Interests Retrieved from [Link]
National Institutes of Health, National Human Genome Research
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article. Institute. (n.d.). Talking glossary of genetic terms. Retrieved
December 31, 2016, from [Link]
Funding Tonkin, E., Calzone, K., Jenkins, J., Lea, D., & Prows, C. (2011).
The author(s) received no financial support for the research, author- Genomic education resources for nursing faculty. Journal of
ship, and/or publication of this article. Nursing Scholarship, 43, 330–340.