Help Me Understand Genetics
Inheriting Genetic Conditions
Reprinted from https://ghr.nlm.nih.gov/
Lister Hill National Center for Biomedical Communications
U.S. National Library of Medicine
National Institutes of Health
Department of Health & Human Services
Published February 27, 2018
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Inheriting Genetic Conditions
Table of Contents
Section Page
What does it mean if a disorder seems to run in my family? 3
Why is it important to know my family medical history? 6
What are the different ways in which a genetic condition can be inherited? 8
If a genetic disorder runs in my family, what are the chances that my 20
children will have the condition?
What are reduced penetrance and variable expressivity? 23
What do geneticists mean by anticipation? 25
What are genomic imprinting and uniparental disomy? 26
Are chromosomal disorders inherited? 28
Why are some genetic conditions more common in particular ethnic 29
groups?
page 2
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
What does it mean if a disorder seems to run in my
family?
A particular disorder might be described as “running in a family” if more than
one person in the family has the condition. Some disorders that affect multiple
family members are caused by gene mutations, which can be inherited (passed
down from parent to child). Other conditions that appear to run in families are
not caused by mutations in single genes. Instead, environmental factors such
as dietary habits or a combination of genetic and environmental factors are
responsible for these disorders.
It is not always easy to determine whether a condition in a family is inherited.
A genetics professional can use a person’s family history (a record of health
information about a person’s immediate and extended family) to help determine
whether a disorder has a genetic component. He or she will ask about the health
of people from several generations of the family, usually first-, second-, and third-
degree relatives.
Degrees of relationship
Degrees of relationship Examples
First-degree relatives Parents, children, brothers, and sisters
Second-degree relatives Grandparents, aunts and uncles, nieces and
nephews, and grandchildren
Third-degree relatives First cousins
page 3
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
This condition affects members in each generation of a family.
For general information about disorders that run in families:
Genetics Home Reference provides consumer-friendly summaries of genetic
conditions (https://ghr.nlm.nih.gov/condition). Each summary includes a brief
description of the condition, an explanation of its genetic cause, and information
about the condition's frequency and pattern of inheritance.
The Coriell Personalized Medicine Collaborative provides a brief introduction
to heritable diseases in the article Heredity: It Runs in the Family (https://
cpmc.coriell.org/genetic-education/it-runs-in-the-family).
page 4
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
The Genetic Science Learning Center at the University of Utah offers interactive
tools about disorders that run in families (http://learn.genetics.utah.edu/content/
history).
The National Human Genome Research Institute offers a brief fact sheet
called Frequently Asked Questions About Genetic Disorders (https://
www.genome.gov/19016930).
The Centre for Genetics Education provides an overview of genetic conditions
(http://www.genetics.edu.au/publications-and-resources/facts-sheets/fact-
sheet-5-genetic-conditions).
page 5
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Why is it important to know my family medical history?
A family medical history is a record of health information about a person and
his or her close relatives. A complete record includes information from three
generations of relatives, including children, brothers and sisters, parents, aunts
and uncles, nieces and nephews, grandparents, and cousins.
Families have many factors in common, including their genes, environment, and
lifestyle. Together, these factors can give clues to medical conditions that may
run in a family. By noticing patterns of disorders among relatives, healthcare
professionals can determine whether an individual, other family members,
or future generations may be at an increased risk of developing a particular
condition.
A family medical history can identify people with a higher-than-usual chance of
having common disorders, such as heart disease, high blood pressure, stroke,
certain cancers, and diabetes. These complex disorders are influenced by a
combination of genetic factors, environmental conditions, and lifestyle choices.
A family history also can provide information about the risk of rarer conditions
caused by mutations in a single gene, such as cystic fibrosis and sickle cell
disease.
While a family medical history provides information about the risk of specific
health concerns, having relatives with a medical condition does not mean that an
individual will definitely develop that condition. On the other hand, a person with
no family history of a disorder may still be at risk of developing that disorder.
Knowing one’s family medical history allows a person to take steps to reduce
his or her risk. For people at an increased risk of certain cancers, healthcare
professionals may recommend more frequent screening (such as mammography
or colonoscopy) starting at an earlier age. Healthcare providers may also
encourage regular checkups or testing for people with a medical condition that
runs in their family. Additionally, lifestyle changes such as adopting a healthier
diet, getting regular exercise, and quitting smoking help many people lower their
chances of developing heart disease and other common illnesses.
The easiest way to get information about family medical history is to talk to
relatives about their health. Have they had any medical problems, and when did
they occur? A family gathering could be a good time to discuss these issues.
Additionally, obtaining medical records and other documents (such as obituaries
and death certificates) can help complete a family medical history. It is important
to keep this information up-to-date and to share it with a healthcare professional
regularly.
page 6
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
For more information about family medical history:
Educational resources related to family health history (https://
geneed.nlm.nih.gov/topic_subtopic.php?tid=5&sid=13) are available from
GeneEd. Additional information about family history (https://medlineplus.gov/
familyhistory.html) is available from MedlinePlus.
The Centers for Disease Control and Prevention's (CDC) Office of Public Health
Genomics provides information about the importance of family medical history
(https://www.cdc.gov/genomics/famhistory/). This resource also includes links to
publications, reports, and tools for recording family health information.
The Office of the Surgeon General offers a tool called My Family Health Portrait
(https://familyhistory.hhs.gov/) that allows you to enter, print, and update your
family health history.
The American Medical Association provides family history tools (https://
www.ama-assn.org/delivering-care/collecting-family-history), including
questionnaires and forms for collecting medical information. The National
Institute on Aging provides suggestions on how to obtain a health history form
older individuals (https://www.nia.nih.gov/health/obtaining-older-patients-medical-
history).
The Genetic Alliance also offers a list of links to family history resources (http://
www.geneticalliance.org/programs/genesinlife/fhh).
page 7
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
What are the different ways in which a genetic
condition can be inherited?
Some genetic conditions are caused by mutations in a single gene. These
conditions are usually inherited in one of several patterns, depending on the
gene involved:
Patterns of inheritance
Inheritance Description Examples
pattern
Autosomal One mutated copy of the gene in each Huntington disease,
dominant cell is sufficient for a person to be affected Marfan syndrome
by an autosomal dominant disorder. In
some cases, an affected person inherits the
condition from an affected parent (image on
page 12). In others, the condition may
result from a new mutation (image on page
13) in the gene and occur in people with
no history of the disorder in their family.
Autosomal In autosomal recessive inheritance (image cystic fibrosis,
recessive on page 14), both copies of the gene in sickle cell disease
each cell have mutations. The parents of
an individual with an autosomal recessive
condition each carry one copy of the
mutated gene, but they typically do not
show signs and symptoms of the condition.
Autosomal recessive disorders are typically
not seen in every generation of an affected
family.
page 8
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Inheritance Description Examples
pattern
X-linked X-linked dominant (image on page 15) fragile X syndrome
dominant disorders are caused by mutations in genes
on the X chromosome, one of the two sex
chromosomes in each cell. In females (who
have two X chromosomes), a mutation in
one of the two copies of the gene in each
cell is sufficient to cause the disorder. In
males (who have only one X chromosome),
a mutation in the only copy of the gene
in each cell causes the disorder. In most
cases, males experience more severe
symptoms of the disorder than females. A
characteristic of X-linked inheritance is that
fathers cannot pass X-linked traits to their
sons (no male-to-male transmission).
X-linked X-linked recessive (image on page 16) hemophilia, Fabry
recessive disorders are also caused by mutations in disease
genes on the X chromosome. In males (who
have only one X chromosome), one altered
copy of the gene in each cell is sufficient to
cause the condition. In females (who have
two X chromosomes), a mutation would
have to occur in both copies of the gene to
cause the disorder. Because it is unlikely
that females will have two altered copies of
this gene, males are affected by X-linked
recessive disorders much more frequently
than females. A characteristic of X-linked
inheritance is that fathers cannot pass X-
linked traits to their sons (no male-to-male
transmission).
Y-linked A condition is considered Y-linked (image Y chromosome
on page 17) if the mutated gene infertility, some
that causes the disorder is located on cases of Swyer
the Y chromosome, one of the two sex syndrome
chromosomes in each of a male's cells.
Because only males have a Y chromosome,
in Y-linked inheritance, a mutation can only
be passed from father to son.
page 9
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Inheritance Description Examples
pattern
Codominant In codominant inheritance (image on page ABO blood group,
18), two different versions (alleles) alpha-1 antitrypsin
of a gene are expressed, and each deficiency
version makes a slightly different protein.
Both alleles influence the genetic trait or
determine the characteristics of the genetic
condition.
Mitochondrial Mitochondrial inheritance (image on page Leber hereditary
19), also known as maternal inheritance, optic neuropathy
applies to genes in mitochondrial DNA. (LHON)
Mitochondria, which are structures in each
cell that convert molecules into energy, each
contain a small amount of DNA. Because
only egg cells contribute mitochondria to
the developing embryo, only females can
pass on mitochondrial mutations to their
children. Conditions resulting from mutations
in mitochondrial DNA can appear in every
generation of a family and can affect both
males and females, but fathers do not pass
these disorders to their daughters or sons.
Many health conditions are caused by the combined effects of multiple genes or
by interactions between genes and the environment. Such disorders usually do
not follow the patterns of inheritance described above. Examples of conditions
caused by multiple genes or gene/environment interactions include heart
disease, diabetes, schizophrenia, and certain types of cancer. For more
information, please see What are complex or multifactorial disorders? (https://
ghr.nlm.nih.gov/primer/mutationsanddisorders/complexdisorders)
Disorders caused by changes in the number or structure of chromosomes
also do not follow the straightforward patterns of inheritance listed above. To
read about how chromosomal conditions occur, please see Are chromosomal
disorders inherited? on page 28
Other genetic factors sometimes influence how a disorder is inherited. For an
example, please see What are genomic imprinting and uniparental disomy? on
page 26
page 10
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
For more information about inheritance patterns:
Resources related to heredity/inheritance patterns (https://geneed.nlm.nih.gov/
topic_subtopic.php?tid=5) and Mendelian inheritance (https://
geneed.nlm.nih.gov/topic_subtopic.php?tid=5&sid=6) are available from GeneEd.
The Centre for Genetics Education provides information about many of the
inheritance patterns outlined above:
• Autosomal dominant inheritance (http://www.genetics.edu.au/
publications-and-resources/facts-sheets/fact-sheet-8-autosomal-
dominant-inheritance)
• Autosomal recessive inheritance (http://www.genetics.edu.au/
publications-and-resources/facts-sheets/fact-sheet-7-autosomal-
recessive-inheritance)
• X-linked dominant inheritance (http://www.genetics.edu.au/
publications-and-resources/facts-sheets/fact-sheet-10-x-linked-
dominant-inheritance)
• X-linked recessive inheritance (http://www.genetics.edu.au/
publications-and-resources/facts-sheets/fact-sheet-9-x-linked-
recessive-inheritance)
• Mitochondrial inheritance (http://www.genetics.edu.au/publications-and-
resources/facts-sheets/fact-sheet-12-mitochondrial-inheritance)
EuroGentest also offers explanations of Mendelian inheritance patterns:
• Autosomal dominant inheritance (http://www.eurogentest.org/
index.php?id=614)
• Autosomal recessive inheritance (http://www.eurogentest.org/
index.php?id=619)
• X-linked inheritance (http://www.eurogentest.org/index.php?id=623)
Additional information about inheritance patterns is available from The Merck
Manual (http://www.merckmanuals.com/professional/special-subjects/general-
principles-of-medical-genetics/single-gene-defects).
page 11
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Images
In this example, a man with an autosomal dominant disorder
has two affected children and two unaffected children.
page 12
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
In this example, a child with an autosomal dominant condition has the
disorder as a result of a new (de novo) mutation that occurred during the
formation of an egg or sperm cell or early in embryonic development.
page 13
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
In this example, two unaffected parents each carry one
copy of a gene mutation for an autosomal recessive
disorder. They have one affected child and three unaffected
children, two of which carry one copy of the gene mutation.
page 14
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
In the example on the left, a father with an X-linked dominant
disorder has two affected daughters and two unaffected sons.
On the right, a mother with an X-linked dominant disorder
has two affected children and two unaffected children.
page 15
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
In the example on the left, a father with an X-linked recessive condition
has two daughters that are carriers of the causative mutation. On
the right, a mother who is a carrier of an X-linked recessive disorder
has one affected son and one daughter who is also a carrier.
page 16
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
In this example, a father with a Y-linked condition
has two affected sons. His daughters are unaffected.
page 17
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
The ABO blood group is a major system for classifying blood types in
humans. Blood type AB is inherited in a codominant pattern. In this
example, a father with blood type A and a mother with blood type B
have four children, each with a different blood type: A, AB, B, and O.
page 18
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
In the family on the left, a woman with a disorder caused by
a mutation in mitochondrial DNA and her unaffected husband
have children who are all affected by the condition. In the family
on the right, a man with a condition resulting from a mutation in
mitochondrial DNA and his unaffected wife have no affected children.
page 19
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
If a genetic disorder runs in my family, what are the
chances that my children will have the condition?
When a genetic disorder is diagnosed in a family, family members often want to
know the likelihood that they or their children will develop the condition. This can
be difficult to predict in some cases because many factors influence a person's
chances of developing a genetic condition. One important factor is how the
condition is inherited. For example:
• Autosomal dominant inheritance: A person affected by an autosomal
dominant disorder (image on page 12) has a 50 percent chance of
passing the mutated gene to each child. The chance that a child will not
inherit the mutated gene is also 50 percent. However, in some cases
an autosomal dominant disorder results from a new (de novo) mutation
(image on page 13) that occurs during the formation of egg or sperm
cells or early in embryonic development. In these cases, the child's
parents are unaffected, but the child may pass on the condition to his
or her own children.
• Autosomal recessive inheritance: Two unaffected people who each
carry one copy of the mutated gene for an autosomal recessive
disorder (image on page 14) (carriers) have a 25 percent chance with
each pregnancy of having a child affected by the disorder. The chance
with each pregnancy of having an unaffected child who is a carrier of
the disorder is 50 percent, and the chance that a child will not have the
disorder and will not be a carrier is 25 percent.
• X-linked dominant inheritance: The chance of passing on an X-
linked dominant condition (image on page 15) differs between men
and women because men have one X chromosome and one Y
chromosome, while women have two X chromosomes. A man passes
on his Y chromosome to all of his sons and his X chromosome to all of
his daughters. Therefore, the sons of a man with an X-linked dominant
disorder will not be affected, but all of his daughters will inherit the
condition. A woman passes on one or the other of her X chromosomes
to each child. Therefore, a woman with an X-linked dominant disorder
has a 50 percent chance of having an affected daughter or son with
each pregnancy.
page 20
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
• X-linked recessive inheritance: Because of the difference in sex
chromosomes, the probability of passing on an X-linked recessive
disorder (image on page 16) also differs between men and women.
The sons of a man with an X-linked recessive disorder will not be
affected, and his daughters will carry one copy of the mutated gene.
With each pregnancy, a woman who carries an X-linked recessive
disorder has a 50 percent chance of having sons who are affected and
a 50 percent chance of having daughters who carry one copy of the
mutated gene.
• Y-linked inheritance: Because only males have a Y chromosome, only
males can be affected by and pass on Y-linked disorders (image on
page 17). All sons of a man with a Y-linked disorder will inherit the
condition from their father.
• Codominant inheritance: In codominant inheritance (image on page
18), each parent contributes a different version of a particular gene,
and both versions influence the resulting genetic trait. The chance of
developing a genetic condition with codominant inheritance, and the
characteristic features of that condition, depend on which versions of
the gene are passed from parents to their child.
• Mitochondrial inheritance: Mitochondria, which are the energy-
producing centers inside cells, each contain a small amount of DNA.
Disorders with mitochondrial inheritance (image on page 19) result
from mutations in mitochondrial DNA. Although these disorders can
affect both males and females, only females can pass mutations in
mitochondrial DNA to their children. A woman with a disorder caused
by changes in mitochondrial DNA will pass the mutation to all of her
daughters and sons, but the children of a man with such a disorder will
not inherit the mutation.
It is important to note that the chance of passing on a genetic condition
applies equally to each pregnancy. For example, if a couple has a child with
an autosomal recessive disorder, the chance of having another child with the
disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not
“protect” future children from inheriting the condition. Conversely, having a child
without the condition does not mean that future children will definitely be affected.
Although the chances of inheriting a genetic condition appear straightforward,
factors such as a person's family history and the results of genetic testing can
sometimes modify those chances. In addition, some people with a disease-
causing mutation never develop any health problems or may experience only
mild symptoms of the disorder. If a disease that runs in a family does not have a
page 21
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
clear-cut inheritance pattern, predicting the likelihood that a person will develop
the condition can be particularly difficult.
Estimating the chance of developing or passing on a genetic disorder can be
complex. Genetics professionals can help people understand these chances and
help them make informed decisions about their health.
For more information about passing on a genetic disorder in a family:
The National Library of Medicine MedlinePlus website offers information about
the chance of developing a genetic disorder on the basis of its inheritance
pattern:
• Autosomal dominant (https://medlineplus.gov/ency/article/002049.htm)
• Autosomal recessive (https://medlineplus.gov/ency/article/002052.htm)
• X-linked dominant (https://medlineplus.gov/ency/article/002050.htm)
• X-linked recessive (https://medlineplus.gov/ency/article/002051.htm)
The Centre for Genetics Education provides an explanation of mitochondrial
inheritance (http://www.genetics.edu.au/publications-and-resources/facts-sheets/
fact-sheet-12-mitochondrial-inheritance).
The Muscular Dystrophy Association explains patterns and probabilities (https://
www.mda.org/sites/default/files/publications/Facts_Genetics_P-210_1.pdf) of
inheritance.
page 22
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
What are reduced penetrance and variable
expressivity?
Reduced penetrance and variable expressivity are factors that influence the
effects of particular genetic changes. These factors usually affect disorders
that have an autosomal dominant pattern of inheritance, although they are
occasionally seen in disorders with an autosomal recessive inheritance pattern.
Reduced penetrance
Penetrance refers to the proportion of people with a particular genetic change
(such as a mutation in a specific gene) who exhibit signs and symptoms of a
genetic disorder. If some people with the mutation do not develop features of
the disorder, the condition is said to have reduced (or incomplete) penetrance.
Reduced penetrance often occurs with familial cancer syndromes. For example,
many people with a mutation in the BRCA1 or BRCA2 gene will develop cancer
during their lifetime, but some people will not. Doctors cannot predict which
people with these mutations will develop cancer or when the tumors will develop.
Reduced penetrance probably results from a combination of genetic,
environmental, and lifestyle factors, many of which are unknown. This
phenomenon can make it challenging for genetics professionals to interpret a
person’s family medical history and predict the risk of passing a genetic condition
to future generations.
Variable expressivity
Although some genetic disorders exhibit little variation, most have signs and
symptoms that differ among affected individuals. Variable expressivity refers
to the range of signs and symptoms that can occur in different people with the
same genetic condition. For example, the features of Marfan syndrome vary
widely— some people have only mild symptoms (such as being tall and thin with
long, slender fingers), while others also experience life-threatening complications
involving the heart and blood vessels. Although the features are highly variable,
most people with this disorder have a mutation in the same gene (FBN1).
As with reduced penetrance, variable expressivity is probably caused by a
combination of genetic, environmental, and lifestyle factors, most of which
have not been identified. If a genetic condition has highly variable signs and
symptoms, it may be challenging to diagnose.
page 23
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
For more information about reduced penetrance and variable expressivity:
The PHG Foundation offers an interactive tutorial on penetrance (http://
www.phgfoundation.org/tutorials/penetrance/) that explains the differences
between reduced penetrance and variable expressivity.
Additional information about penetrance and expressivity (http://
www.merckmanuals.com/home/fundamentals/genetics/inheritance-of-single-
gene-disorders) is available from the Merck Manual Home Health Handbook for
Patients & Caregivers.
page 24
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
What do geneticists mean by anticipation?
The signs and symptoms of some genetic conditions tend to become more
severe and appear at an earlier age as the disorder is passed from one
generation to the next. This phenomenon is called anticipation. Anticipation is
most often seen with certain genetic disorders of the nervous system, such as
Huntington disease, myotonic dystrophy, and fragile X syndrome.
Anticipation typically occurs with disorders that are caused by an unusual type
of mutation called a trinucleotide repeat expansion. A trinucleotide repeat is a
sequence of three DNA building blocks (nucleotides) that is repeated a number
of times in a row. DNA segments with an abnormal number of these repeats
are unstable and prone to errors during cell division. The number of repeats
can change as the gene is passed from parent to child. If the number of repeats
increases, it is known as a trinucleotide repeat expansion. In some cases, the
trinucleotide repeat may expand until the gene stops functioning normally. This
expansion causes the features of some disorders to become more severe with
each successive generation.
Most genetic disorders have signs and symptoms that differ among affected
individuals, including affected people in the same family. Not all of these
differences can be explained by anticipation. A combination of genetic,
environmental, and lifestyle factors is probably responsible for the variability,
although many of these factors have not been identified. Researchers study
multiple generations of affected family members and consider the genetic cause
of a disorder before determining that it shows anticipation.
For more information about anticipation:
The Merck Manual for Healthcare Professionals provides a brief explanation
of anticipation as part of its chapter on nontraditional inheritance (http://
www.merckmanuals.com/professional/special-subjects/general-principles-of-
medical-genetics/unusual-aspects-of-inheritance).
The Myotonic Dystrophy Foundation describes anticipation in the context of
myotonic dystrophy (http://www.myotonic.org/what-dm/disease-mechanism).
(Click on the tab that says "Anticipation.")
page 25
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
What are genomic imprinting and uniparental disomy?
Genomic imprinting and uniparental disomy are factors that influence how some
genetic conditions are inherited.
Genomic imprinting
People inherit two copies of their genes—one from their mother and one from
their father. Usually both copies of each gene are active, or “turned on,” in cells.
In some cases, however, only one of the two copies is normally turned on.
Which copy is active depends on the parent of origin: some genes are normally
active only when they are inherited from a person’s father; others are active only
when inherited from a person’s mother. This phenomenon is known as genomic
imprinting.
In genes that undergo genomic imprinting, the parent of origin is often marked,
or “stamped,” on the gene during the formation of egg and sperm cells. This
stamping process, called methylation, is a chemical reaction that attaches small
molecules called methyl groups to certain segments of DNA. These molecules
identify which copy of a gene was inherited from the mother and which was
inherited from the father. The addition and removal of methyl groups can be used
to control the activity of genes.
Only a small percentage of all human genes undergo genomic imprinting.
Researchers are not yet certain why some genes are imprinted and others are
not. They do know that imprinted genes tend to cluster together in the same
regions of chromosomes. Two major clusters of imprinted genes have been
identified in humans, one on the short (p) arm of chromosome 11 (at position
11p15) and another on the long (q) arm of chromosome 15 (in the region 15q11
to 15q13).
Uniparental disomy
Uniparental disomy (UPD) occurs when a person receives two copies of a
chromosome, or part of a chromosome, from one parent and no copies from the
other parent. UPD can occur as a random event during the formation of egg or
sperm cells or may happen in early fetal development.
In many cases, UPD likely has no effect on health or development. Because
most genes are not imprinted, it doesn’t matter if a person inherits both copies
from one parent instead of one copy from each parent. In some cases, however,
it does make a difference whether a gene is inherited from a person’s mother
or father. A person with UPD may lack any active copies of essential genes
that undergo genomic imprinting. This loss of gene function can lead to delayed
development, intellectual disability, or other health problems.
page 26
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Several genetic disorders can result from UPD or a disruption of normal genomic
imprinting. The most well-known conditions include Prader-Willi syndrome, which
is characterized by uncontrolled eating and obesity, and Angelman syndrome,
which causes intellectual disability and impaired speech. Both of these disorders
can be caused by UPD or other errors in imprinting involving genes on the
long arm of chromosome 15. Other conditions, such as Beckwith-Wiedemann
syndrome (a disorder characterized by accelerated growth and an increased risk
of cancerous tumors), are associated with abnormalities of imprinted genes on
the short arm of chromosome 11.
For more information about genomic imprinting and UPD:
The National Human Genome Research Institute provides a definition of genetic
imprinting (https://www.genome.gov/glossary/index.cfm?id=92) in its Talking
Glossary of Genetic Terms.
The University of Utah offers a basic overview of genomic imprinting (http://
learn.genetics.utah.edu/content/epigenetics/imprinting/).
Additional information about epigenetics, including genomic imprinting (http://
www.genetics.edu.au/publications-and-resources/facts-sheets/fact-sheet-14-
epigenetics) is available from the Centre for Genetics Education.
Geneimprint, a website about genomic imprinting, provides an introduction to
imprinting (http://www.geneimprint.com/site/what-is-imprinting)as well as related
articles and a list of imprinted genes (http://www.geneimprint.com/site/genes-by-
species).
An animated tutorial from the University of Miami illustrates how uniparental
disomy occurs (http://hihg.med.miami.edu/code/http/modules/education/Design/
animate/uniDisomy.htm).
page 27
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Are chromosomal disorders inherited?
Although it is possible to inherit some types of chromosomal abnormalities, most
chromosomal disorders (such as Down syndrome and Turner syndrome) are not
passed from one generation to the next.
Some chromosomal conditions are caused by changes in the number of
chromosomes. These changes are not inherited, but occur as random events
during the formation of reproductive cells (eggs and sperm). An error in cell
division called nondisjunction results in reproductive cells with an abnormal
number of chromosomes. For example, a reproductive cell may accidentally
gain or lose one copy of a chromosome. If one of these atypical reproductive
cells contributes to the genetic makeup of a child, the child will have an extra or
missing chromosome in each of the body’s cells.
Changes in chromosome structure can also cause chromosomal disorders.
Some changes in chromosome structure can be inherited, while others occur
as random accidents during the formation of reproductive cells or in early fetal
development. Because the inheritance of these changes can be complex, people
concerned about this type of chromosomal abnormality may want to talk with a
genetics professional.
Some cancer cells also have changes in the number or structure of their
chromosomes. Because these changes occur in somatic cells (cells other than
eggs and sperm), they cannot be passed from one generation to the next.
For more information about how chromosomal changes occur:
As part of its fact sheet on chromosome abnormalities, the National Human
Genome Research Institute provides a discussion of how chromosome
abnormalities happen. (https://www.genome.gov/11508982#6)
The Chromosome Disorder Outreach fact sheet Introduction to Chromosomes
(https://chromodisorder.org/introduction-to-chromosomes/) explains how
structural changes occur.
The March of Dimes discusses the causes of chromosomal abnormalities in
their fact sheet Chromosomal Conditions (http://www.marchofdimes.org/baby/
chromosomal-conditions.aspx).
Additional information about how chromosomal changes happen
(https://www.urmc.rochester.edu/encyclopedia/content.aspx?
ContentTypeID=90&ContentID=P02126) is available from the University of
Rochester Medical Center.
page 28
Genetics Home Reference - https://ghr.nlm.nih.gov/
Inheriting Genetic Conditions
Why are some genetic conditions more common in
particular ethnic groups?
Some genetic disorders are more likely to occur among people who trace their
ancestry to a particular geographic area. People in an ethnic group often share
certain versions of their genes, which have been passed down from common
ancestors. If one of these shared genes contains a disease-causing mutation, a
particular genetic disorder may be more frequently seen in the group.
Examples of genetic conditions that are more common in particular ethnic groups
are sickle cell disease, which is more common in people of African, African
American, or Mediterranean heritage; and Tay-Sachs disease, which is more
likely to occur among people of Ashkenazi (eastern and central European)
Jewish or French Canadian ancestry. It is important to note, however, that these
disorders can occur in any ethnic group.
For more information about genetic disorders that are more common in
certain groups:
Know Your Genes from the Genetic Disease Foundation offers a list
and descriptions of genetic disorders (http://www.knowyourgenes.org/
genetic_diseases.shtml) that occur more frequently in people of various ethnic
groups.
The Norton & Elaine Sarnoff Center for Jewish Genetics provides information
on disorders that occur more frequently in people with Jewish ancestry,
including genetic traits that tend to be more common in Ashkenazi Jews (http://
www.jewishgenetics.org/cjg/Ashkenazi-Jewish-Disorders.aspx) and Sephardic
Jews (http://www.jewishgenetics.org/cjg/Sephardic-Jewish-Disorders.aspx).
page 29
https://ghr.nlm.nih.gov/
Lister Hill National Center for Biomedical Communications
U.S. National Library of Medicine
National Institutes of Health
Department of Health & Human Services
Published on February 27, 2018
