Chromosomal abnormalities occur when there is a defect in a chromosome, or in the arrangement of the genetic material on the

chromosome. Very often, chromosome abnormalities give rise to specific physical symptoms, however, the severity of these can
vary from individual to individual.

Abnormalities can be in the form of additional material which may be attached to a chromosome, or where part or a whole
chromosome is missing, or even in defective formation of a chromosome. Any increases or decreases in chromosomal material
interfere with normal development and function.

There are two main types of chromosomal abnormality which can occur during meiosis and fertilization: numerical aberrations and
structural aberrations.

Numerical Aberrations
These are usually caused by a failure of chromosome division, which results in cells with an extra chromosome or a deficiency in
chromosomes.

Gametes with these anomalies can result in conditions such as Down syndrome (who have 47 chromosomes instead of 46), or
Turner syndrome (45 chromosomes). Common types of numerical aberrations are: triploidy, trisomy, monosomy and mosaicism.

Structural Aberrations

These occur due to a loss or genetic material, or a rearrangement in the location of the genetic material. They include: deletions,
duplications, inversions, ring formations, and translocations.

 Deletions: A portion of the chromosome is missing or deleted. Known disorders include Wolf-Hirschhorn syndrome, which is caused
by partial deletion of the short arm of chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder.

 Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material. Known disorders include Charcot-
Marie-Tooth disease type 1A which may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on
chromosome 17.

 Translocations: When a portion of one chromosome is transferred to another chromosome. There are two main types of
translocations. In a reciprocal translocation, segments from two different chromosomes have been exchanged. In a Robertsonian
translocation, an entire chromosome has attached to another at the centromere; these only occur with chromosomes 13, 14, 15, 21
and 22.

 Inversions: A portion of the chromosome has broken off, turned upside down and reattached, therefore the genetic material is
inverted.

 Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic
material.

 Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere.

Structural aberrations also include some disorders which are characterized by chromosomal instability and breakage. One example,
is the creation of a fragile site on the X Chromosome - Fragile X syndrome. Boys are worse affected by this because they only have
one X-Chromosome but even in girls, Fragile X syndrome can cause learning difficulties.

Most chromosome anomalies occur as an accident in the egg or sperm, and are therefore not inherited. The anomaly is present in
every cell of the body.Some anomalies, however, can happen after conception, resulting in mosaicism (where some cells have the
anomaly and some do not). Chromosome anomalies can be inherited from a parent or be "de novo". This is why chromosome
studies are often performed on parents when a child is found to have an anomaly
.

How many chromosomes do humans have?

The typical number of chromosomes in a human cell is 46: 23 pairs, holding an estimated total of 20,000 to 25,000 genes. One set of
23 chromosomes is inherited from the biological mother (from the egg), and the other set is inherited from the biological father
(from the sperm).

Of the 23 pairs of chromosomes, the first 22 pairs are called "autosomes." The final pair is called the "sex chromosomes." Sex
chromosomes determine an individual's sex: females have two X chromosomes (XX), and males have an X and a Y chromosome (XY).
The mother and father each contribute one set of 22 autosomes and one sex chromosome.

How do scientists study chromosomes?

For a century, scientists studied chromosomes by looking at them under a microscope. In order for chromosomes to be seen this
way, they need to be stained. Once stained, the chromosomes look like strings with light and dark "bands," and their picture can be
taken. A picture, or chromosome map, of all 46 chromosomes is called a karyotype. The karyotype can help identify abnormalities in
the structure or the number of chromosomes.

To help identify chromosomes, the pairs have been numbered from 1 to 22, with the 23rd pair labeled "X" and "Y." In addition, the
bands that appear after staining are numbered; the higher the number, the farther that area is from the centromere.

In the past decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal
abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA sample. The
comparison can be used to find chromosomal abnormalities where the two samples differ.

One such method is called noninvasive prenatal testing. This is a test to screen a pregnancy to determine whether a baby has an
increased chance of having specific chromosome disorders. The test examines the baby's DNA in the mother's blood.

What are chromosome abnormalities?

There are many types of chromosome abnormalities. However, they can be organized into two basic groups: numerical
abnormalities and structural abnormalities.

 Numerical Abnormalities: When an individual is missing one of the chromosomes from a pair, the condition is called
monosomy. When an individual has more than two chromosomes instead of a pair, the condition is called trisomy.

An example of a condition caused by numerical abnormalities is Down syndrome, which is marked by mental retardation, learning
difficulties, a characteristic facial appearance and poor muscle tone (hypotonia) in infancy. An individual with Down syndrome has
three copies of chromosome 21 rather than two; for that reason, the condition is also known as Trisomy 21. An example of
monosomy, in which an individual lacks a chromosome, is Turner syndrome. In Turner syndrome, a female is born with only one sex
chromosome, an X, and is usually shorter than average and unable to have children, among other difficulties.

 Structural Abnormalities: A chromosome's structure can be altered in several ways.

 Deletions: A portion of the chromosome is missing or deleted.
 Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material.
 Translocations: A portion of one chromosome is transferred to another chromosome. There are two main types of
translocation. In a reciprocal translocation, segments from two different chromosomes have been exchanged. In a
Robertsonian translocation, an entire chromosome has attached to another at the centromere.
 Inversions: A portion of the chromosome has broken off, turned upside down, and reattached. As a result, the
genetic material is inverted.
  Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss
of genetic material.

Most chromosome abnormalities occur as an accident in the egg or sperm. In these cases, the abnormality is present in every cell of
the body. Some abnormalities, however, happen after conception; then some cells have the abnormality and some do not.

Chromosome abnormalities can be inherited from a parent (such as a translocation) or be "de novo" (new to the individual). This is
why, when a child is found to have an abnormality, chromosome studies are often performed on the parents.

How do chromosome abnormalities happen?

Chromosome abnormalities usually occur when there is an error in cell division. There are two kinds of cell division, mitosis and
meiosis.

 Mitosis results in two cells that are duplicates of the original cell. One cell with 46 chromosomes divides and becomes two
cells with 46 chromosomes each. This kind of cell division occurs throughout the body, except in the reproductive organs.
This is the way most of the cells that make up our body are made and replaced.
 Meiosis results in cells with half the number of chromosomes, 23, instead of the normal 46. This is the type of cell division
that occurs in the reproductive organs, resulting in the eggs and sperm.

In both processes, the correct number of chromosomes is supposed to end up in the resulting cells. However, errors in cell division
can result in cells with too few or too many copies of a chromosome. Errors can also occur when the chromosomes are being
duplicated.

Other factors that can increase the risk of chromosome abnormalities are:

 Maternal Age: Women are born with all the eggs they will ever have. Some researchers believe that errors can crop up in
the eggs' genetic material as they age. Older women are at higher risk of giving birth to babies with chromosome
abnormalities than younger women. Because men produce new sperm throughout their lives, paternal age does not
increase risk of chromosome abnormalities.
 Environment: Although there is no conclusive evidence that specific environmental factors cause chromosome
abnormalities, it is still possible that the environment may play a role in the occurrence of genetic errors.

Almost every cell in our body contains 23 pairs of chromosomes, for a total of 46 chromosomes. Half of the chromosomes come
from our mother, and the other half come from our father. The first 22 pairs are called autosomes. The 23rd pair consists of the sex
chromosomes, X and Y. Females usually have two X chromosomes, and males usually have one X and one Y chromosome in each
cell. All of the information that the body needs to grow and develop comes from the chromosomes. Each chromosome contains
thousands of genes, which make proteins that direct the body’s development, growth, and chemical reactions.

Many types of chromosomal abnormalities exist, but they can be categorized as either numerical or structural. Numerical
abnormalities are whole chromosomes either missing from or extra to the normal pair. Structural abnormalities are when part of an
individual chromosome is missing, extra, switched to another chromosome, or turned upside down.
Chromosomal abnormalities can occur as an accident when the egg or the sperm is formed or during the early developmental stages
of the fetus. The age of the mother and certain environmental factors may play a role in the occurrence of genetic errors. Prenatal
screening and testing can be performed to examine the chromosomes of the fetus and detect some, but not all, types of
chromosomal abnormalities.

Chromosomal abnormalities can have many different effects, depending on the specific abnormality. For example, an extra copy of
chromosome 21 causes Down syndrome (trisomy 21). Chromosomal abnormalities can also cause miscarriage, disease, or problems
in growth or development.

The most common type of chromosomal abnormality is known as aneuploidy, an abnormal chromosome number due to an extra or
missing chromosome.Most people with aneuploidy have trisomy (three copies of a chromosome) instead of monosomy (single copy
of a chromosome). Down syndrome is probably the most well-known example of a chromosomal aneuploidy. Besides trisomy 21,
the major chromosomal aneuploidies seen in live-born babies are: trisomy 18; trisomy 13; 45, X (Turner syndrome); 47, XXY
(Klinefelter syndrome); 47, XYY; and 47, XXX.

Structural chromosomal abnormalities result from breakage and incorrect rejoining of chromosomal segments. A range of structural
chromosomal abnormalities result in disease. Structural rearrangements are defined as balanced if the complete chromosomal set is
still present, though rearranged, and unbalanced if information is additional or missing. Unbalanced rearrangements include
deletions, duplications, or insertions of a chromosomal segment. Ring chromosomes can result when a chromosome undergoes two
breaks and the broken ends fuse into a circular chromosome. An isochromosome can form when an arm of the chromosome is
missing and the remaining arm duplicates.

Balanced rearrangements include inverted or translocated chromosomal regions. Since the full complement of DNA material is still
present, balanced chromosomal rearrangements may go undetected because they may not result in disease. A disease can arise as a
result of a balanced rearrangement if the breaks in the chromosomes occur in a gene, resulting in an absent or nonfunctional
protein, or if the fusion of chromosomal segments results in a hybrid of two genes, producing a new protein product whose function
is damaging to the cell.

Examples of chromosomal disorders

Some of the most common chromosomal abnormalities include:

 Down's syndrome or trisomy 21

 Edward's syndrome or trisomy 18
 Patau syndrome or trisomy 13
 Cri du chat syndrome or 5p minus syndrome (partial deletion of short arm of chromosome 5)
 Wolf-Hirschhorn syndrome or deletion 4p syndrome
 Jacobsen syndrome or 11q deletion disorder
 Klinefelter's syndrome or presence of additional X chromosome in males
 Turner syndrome or presence of only a single X chromosome in females
 XYY syndrome and XXX syndrome
URMC / Encyclopedia / Medical Genetics: Types of Genetic Changes

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Medical Genetics: Types of Genetic Changes

The human body has about 20,000 different genes in each cell. Genes are located on chromosomes, which are stick-shaped
structures in the middle of the cell (nucleus) . Each cell usually has 46 chromosomes grouped in 23 pairs. Each gene has a specific
function. And when a gene or chromosome is abnormal, it may cause health problems in the body.

There are 2 main types of genetic changes:

Chromosome abnormalities

Single-gene defects

What are chromosome abnormalities?

Chromosome abnormalities in the baby may be inherited from the parent or may occur with no family history. These are the most
common:

Aneuploidy

This means there are more or fewer chromosomes than the normal number. Examples include:

Down syndrome (trisomy 21). Cells contain 3 copies of the 21st chromosome.

Turner syndrome. One of the 2 sex chromosomes is not transferred. This leaves a single X chromosome for 45 total chromosomes
instead of 46.

Deletion

This is when part of a chromosome is missing, or part of the DNA code is missing.

Inversion
This is when a chromosome breaks and the piece of it turns around and reattaches itself. Inversions can be passed down in families,
but they may or may not cause birth defects.

Ring

A ring chromosome is one where the ends are attached to itself to form a ring. Rings can be passed down in families. They may or
may not cause health problems.

Translocation

This is when a chromosome segment rearranges from one location to another. It can happen either within the same chromosome or
move to another chromosome. There are 2 types:

Balanced translocation. This is when the DNA is equally exchanged between chromosomes. No DNA is lost or added. A parent with a
balanced translocation is healthy, but he or she may be at risk for passing on unbalanced chromosomes to a child.

Robertsonian translocation. This is a balanced translocation in which 1 chromosome joins the end of another.

Mosaicism

This is when a person has 2 or more sets of chromosomes in his or her cells with different genetic material.

What are single-gene changes?

A change in a single gene causes a defect or abnormality. Single-gene changes usually have a higher risk of being passed on to
children. Single-gene changes can be:

Dominant

This means the abnormality occurs when only 1 of the genes from 1 parent is abnormal. If the parent has the disorder, the baby has
a 1 in 2 chance of inheriting it. Examples include:

Achondroplasia. This is a bone development disorder that causes dwarfism.

Marfan syndrome. This is a connective tissue disorder that causes long limbs and heart defects.

Recessive
This means the abnormality only occurs when both parents have a copy of an abnormal gene. If both parents are carriers, a baby has
a 1 in 4 chance of having the disorder. Examples include:

Cystic fibrosis. This is a disorder of the glands that causes excess mucus in the lungs. It also causes problems with how the pancreas
works and with how food is absorbed.

Sickle cell disease. This condition causes abnormal red blood cells that don’t carry oxygen normally.

Tay-Sachs disease. This is an inherited condition that causes the central nervous system to decline. The condition is fatal, usually by
age 5.

X-linked

The disorder is determined by genes on the X chromosome. Males are mainly affected and have the disorder. Daughters of men with
the disorder are carriers of the trait and have a 1 in 2 chance of passing it to their children. Sons of women who are carriers each
have a 1 in 2 chance of having the disorder. Examples include:

Duchenne muscular dystrophy. This is a disease that causes muscle wasting.

Hemophilia. This is a bleeding disorder caused by low levels or lack of a blood protein that is needed for clotting.

How genetic changes are passed along in a family

The way a gene is inherited can help determine the risk of it in a current or future pregnancy. The risk of having a baby with a birth
defect from a genetic change increases if:

The parents have another child with a genetic disorder.

There is a family history of a genetic disorder.

One parent has a chromosome abnormality.

The baby in the womb has abnormalities seen on an ultrasound.

Families at risk for genetic diseases may want to talk with a certified genetic counselor. Making a chart of the family members and
their health histories can help show risks for certain problems. Genetic counseling also helps parents understand the effects of a
disorder and ways it may be prevented or treated.

Getting genetic testing

Each parent's DNA may need to be checked. This is done to learn about some genetic inheritance patterns. Prenatal testing can also
be done to check the baby in the womb for problems. Testing may include:

Ultrasound. This test uses sound waves to look at how a baby in the womb is growing.

Chorionic villus sampling (CVS). This test uses a sample of tissues around the baby to look for problems.

Amniocentesis. This test uses a sample of the amniotic fluid from the sac around the baby to check for problems.

Noninvasive prenatal screening. This test involves taking a blood sample from the mother to look for chromosome differences, such
as aneuploidy.

Carrier screening. This test uses a sample of blood from each parent to check if they carry genetic changes for certain genetic
conditions.