Department of Botany

Chromosomal
Aberrations

Government College University GENETICS-3203

Lahore

Submitted to: Dr. Memuna Submitted by: Zainab Asgher

Ghafoor Shahid 0141-BH-BOT-20
May, 2023
Table of Contents
Introduction: ................................................................................................................................................. 2
Types of Chromosomal Aberrations: ............................................................................................................ 2
Numerical Chromosomal Aberrations ...................................................................................................... 2
 Aneuploidy: ................................................................................................................................... 2
 Polyploidy ...................................................................................................................................... 3
Structural Chromosomal Aberrations: ...................................................................................................... 4
Causes of Chromosomal Abnormalities ........................................................................................................ 7
Effects of Chromosomal Aberrations: ........................................................................................................... 7
 Genetic disorders: ............................................................................................................................. 7
Down syndrome .................................................................................................................................... 7
Turner syndrome .................................................................................................................................. 8
Klinefelter syndrome............................................................................................................................. 8
Cri du chat syndrome ............................................................................................................................ 8
Williams’s syndrome ............................................................................................................................. 9
Prader-Willi syndrome .......................................................................................................................... 9
Angelman syndrome ............................................................................................................................. 9
CANCER: .................................................................................................................................................... 9
Diagnosis of Chromosomal Aberrations ..................................................................................................... 10
Karyotyping ............................................................................................................................................. 10
“Fluorescence In Situ Hybridization (FISH)” ............................................................................................ 10
Array Comparative Genomic Hybridization (aCGH): ............................................................................... 11
Treatment ................................................................................................................................................... 11
Gene Therapy .......................................................................................................................................... 11
“Bone Marrow Transplantation” ............................................................................................................ 11
Enzyme Replacement Therapy: .............................................................................................................. 11
Supportive Care: ..................................................................................................................................... 12
Conclusion: .................................................................................................................................................. 12
References: ................................................................................................................................................. 13
Chromosomal Aberrations
Introduction:
Chromosome aberrations are changes to the shape or quantity of chromosomes in a cell of an
organism. These alterations may result from chemical imbalances that disrupt chromosomal
integrity during cell division or they may be brought on by environmental factors like radiation
exposure and specific poisons. Such changes can lead to a wide range of symptoms and health
issues, including birth defects, infertility, developmental delays, and shortened lifespan. In some
cases, chromosome aberrations may create new mutations which result in increased fitness for
affected individuals compared with those without anomalies. While research into the causes and
effects of aberration is ongoing, it remains one of the most important areas of study when
considering genetic risk factors associated with medical conditions across all species from plants
to humans. Furthermore, the continued investigation will play an essential role if we wished to
develop advanced treatments capable of correcting abnormal genome arrangements before
conception or soon after fertilization occurs.

Types of Chromosomal Aberrations:

Chromosome aberrations are abnormalities that occur in

 Number of chromosomes.
 The Structure

Numerical Chromosomal Aberrations

Other than 2n and n, certain organisms exhibit polyploidy, or having more than two sets of
chromosomes. Polyploidy is common in plant species but unusual in higher mammals.
Aneuploidy, on the other hand, is a state in which one or more chromosomes—or parts of
chromosomes—are added or removed. In both polyploidy and aneuploidy, the chromosome
number is abnormal.

 Aneuploidy:
An abnormally excessive amount of chromosomes in a cell is known as aneuploidy, which can
result in genetic disorders and developmental abnormalities. Aneuploidy occurs due to the failure
of chromosome segregation during cell division.
There are two types of aneuploidy:

i. Monosomy: A kind of aneuploidy known as monosomy occurs when a cell contains one
copy of a certain chromosome rather than the usual two copies. Any chromosome can
experience monosomy, but most often occurs in chromosomes X and Y. Monosomy is
 usually lethal in humans, but Turner syndrome is an example of a survivable monosomy
disorder, in which females have only one X chromosome instead of two.

Figure 1: Example of monosomy (one chromosome missing)

ii. Trisomy: An additional copy of a specific chromosome is present in each cell in a condition
known as trisomy, resulting in three copies instead of the normal two copies. Trisomy can
occur in any chromosome, but the most common trisomy disorders are “trisomy 21, 18,
and 13”. The most typical trisomy disorder is trisomy 21, or Down syndrome, in which
individuals have three copies of chromosome 21. Trisomy 18 and trisomy 13 are less
common and usually result in severe developmental abnormalities and early mortality.

Figure 2: Trisomy types and examples a) trisomy 13 b) trisomy 18 c) trisomy 21

 Polyploidy
When an organism contains more than two whole sets of chromosomes in each of its cells, it is
said to be polyploid. The terms autopolyploidy and allopolyploidy are used to describe the two
forms of polyploidy.

i. Auto polyploidy: In autopolyploidy, more than two distinct sets of chromosomes make up
an organism that are identical or nearly identical in their structure and genetic content.
Autopolyploidy can occur due to the failure of cell division during mitosis or meiosis,
resulting in the doubling of the chromosomes in a cell. This type of polyploidy is common
in plants, and it can lead to the evolution of new species.
 Figure 3: Formation of autopolyploid

ii. Allo polyploidy: In allopolyploidy, More than two distinct sets of chromosomes from
several species make up an organism. Allopolyploidy can occur due to hybridization
between two different species, followed by a failure of cell division during mitosis or
meiosis. This type of polyploidy is also common in plants, and it can lead to the evolution
of new species with unique genetic characteristics.

Figure 4: Formation of allopolyploids

The evolution of numerous plant species has been significantly influenced by both autopolyploidy
and allopolyploidy. In fact, many of the crops we rely on today, such as wheat, cotton, and tobacco,
are the result of polyploidization events that occurred during their evolutionary history.

Structural Chromosomal Aberrations:

There are four main types: deletions, duplications, translocations, and inversions.

i. Deletion is a type of chromosome aberration defined by partial or total loss of genetic

material on one's chromosomes. This occurs when part or all of the DNA contained in a
certain segment isn’t replicated properly during meiosis and results in missing genes from
 that region. The most common symptom associated with this
chromosomal defect is abnormal physical features, cognitive
defects as well as significant medical conditions such as
cancer and Down syndrome among others. Deletion
mutations can be caused by an array of external factors
including radiation exposure, environmental contaminants
(chemicals), structural disruptions due to age, etc., although
their exact mechanism remains unknown at the present
timeframe.
Examples that are frequently used include Cri-du-Chat
Syndrome (triggered by a deletion at 5p) and Prader-Willi
Syndrome (caused by deletion at 15q). Other effects caused
by such irregularities may include severe mental retardation
Figure 5: Deletion of chromosome
as well as physical malformations.

Treatment may involve subjecting patients to chemotherapy depending on the severity of

the mutation and its associated symptoms/complications.
ii. A duplication type of chromosomal aberration is when a copy of part or the entire
chromosome is formed during cell division. This can lead to an increase in gene dosage,
which may result in changes that disrupt normal cell function and cause genetic disorders.
Duplication abnormalities involve both autosomes as well as sex chromosomes and can
range from very small duplications (a few hundred base pairs) to ones affecting millions of
base pairs.

The precise clinical result of a duplication relies on the

abnormality's form, location, size, and degree, as it affects
different genes at different levels. Depending upon these
factors, some symptoms associated with this type of
disorder include delayed development; facial anomalies;
physical features like short stature or disfigurement;
musculoskeletal problems; cognitive difficulties such as
mental retardation, autism spectrum disorder, etc.; organ
dysfunction due to abnormal growths caused by disrupted
genes within organs (like skin Problems).
Figure 6: Duplication of chromosome
iii. Translocations are a type of chromosomal aberration where DNA from one chromosome
is moved to another non-homologous pair. They can be balanced or unbalanced depending
on the size and number of chromosomes involved in the process. In balanced
translocations, fragments of two different chromosomes exchange places through breakage
and reunion at new loci known as reciprocal recombination. During an unbalanced
rearrangement, some material is lost due to unequal crossing over which results in more
genetic material being transferred from one chromosome compared to its homologous
counterpart. These structural alterations affect gene expression resulting in abnormal
phenotypes ranging from subtle changes such as infertility or learning disabilities up to
severe syndromes like Down syndrome caused by trisomy 21.

Figure 7: Balanced translocation of chromosome

iv. Inversion is a type of chromosomal aberration that occurs when a chromosome breaks in
two parts and the broken ends reattach in reverse (inverted) order relative to their original
orientation. This rearrangement causes deletions, duplications, or translocations within the
inverted region but leaves regional gene arrangement unaffected overall. Depending upon
its position, it can affect various regions across multiple chromosomes leading to different
clinical phenotypes such as infertility and miscarriages due to abnormal gametes;
developmental anomalies - physical features, mental retardation/learning disabilities;
cancer predisposition, etc.

Figure 8; Inversion of chromosome

 Diagnosis usually involves karyotyping which reveals an inverse pattern on gel
electrophoresis for most cases, however, some special techniques like fluorescent in situ
hybridization (FISH) may be required in specific scenarios where traditional methods
cannot detect abnormalities/mutations effectively.

Causes of Chromosomal Abnormalities

Normal chromosome aberrations are caused by accidents during DNA replication and cell
division. Numerous factors, including genetic and environmental ones, can cause these changes.
Environmental aspects that can contribute to chromosomal aberrations include exposure to
radiation, certain chemicals, and other agents. These agents can cause changes in the cell’s genetic
material, resulting in an abnormality in chromosome structure or number.

Genetic factors can also cause chromosomal aberrations. Mutations in the genes can lead to
chromosome structure or number changes, resulting in an abnormality. This can be caused by
inheritance, or it can be due to a mutation during the development of the organism.

In conclusion, numerous genetic and environmental variables can result in chromosomal

abnormalities. Radiation exposure, certain chemicals, viruses, and mutations can all contribute to
chromosomal aberrations.

Effects of Chromosomal Aberrations:

 Genetic disorders:
Here are some genetic disorders or syndromes caused by chromosomal aberrations:

Down syndrome: A second copy of chromosome 21 results in Down syndrome. This condition is
characterized by intellectual disability, distinct facial features, and developmental delays.

Figure 9: Down syndrome baby

Turner syndrome: In females, a missing or imperfect X chromosome results in Turner syndrome.
This condition can result in short stature, infertility, and heart defects.

Figure 10: Turner syndrome baby

Klinefelter syndrome: In males, an extra copy of the X chromosome results in Klinefelter

syndrome. This condition can result in infertility, reduced testosterone levels, and developmental
delays.

Figure 11: Klinefelter syndrome XXY

Cri du chat syndrome: A loss on chromosome 5 is the cause of the Cri du Chat syndrome. This
condition can result in intellectual disability, developmental delays, and distinct facial features.
 Figure 12: Baby having Cri du Chat syndrome

Williams’s syndrome: On chromosome 7, there is a loss that leads to Williams' syndrome. This
condition can result in intellectual disability, cardiovascular problems, and distinctive facial
features.

Prader-Willi syndrome: A loss on chromosome 15 is the cause of Prader-Willi syndrome. This

condition can result in intellectual disability, behavioral problems, and a chronic feeling of hunger.

Angelman syndrome: A loss on chromosome 15 is the root cause of Angelman syndrome. This
condition can result in intellectual disability, developmental delays, and seizures.

These are just a few examples of syndromes caused by chromosomal aberrations. Changes in
chromosomal number or shape also contribute to a wide variety of additional genetic diseases.

CANCER:
The onset and spread of cancer are significantly influenced by chromosomal abnormalities. Cancer
cells often acquire chromosomal abnormalities, including deletions, duplications, inversions,
translocations, and aneuploidy, which lead to the activation or inactivation of oncogenes or tumor
suppressor genes.

Chromosomal aberrations can cause several changes in the genetic material of cells that promote
the growth and survival of cancer cells. These changes include:

Activation of Oncogenes: Chromosomal aberrations can activate oncogenes, which are genes that
promote cell growth and division. BCR and ABL gene translocation in “chronic myelogenous
leukaemia”, for instance (CML) leads to the activation of the BCR-ABL oncogene, which drives
the proliferation of cancer cells.
Inactivation of Tumor Suppressor Genes: Chromosomal aberrations can also cause the loss or
inactivation of cancer-suppressing genes, which are genes that often stop the growth of cells and
encourage cell death, preventing the development of cancer. For example, the loss of the tumor
suppressor gene TP53 in many cancers, including breast, lung, and colorectal cancer, leads to
uncontrolled cell growth.
Chromosomal Instability: Chromosomal aberrations can also cause chromosomal instability,
which is a condition where cells have an abnormal number or structure of chromosomes. This
instability can lead to further genetic changes and the accumulation of additional mutations that
promote cancer development.

In conclusion, chromosomal abnormalities can encourage oncogene activation, tumour moderator

gene deactivation, and chromosomal instability, which can all contribute to the onset and spread
of cancer. Understanding the role of chromosomal aberrations in cancer is crucial for developing
new targeted therapies and improving cancer treatment outcomes.

Diagnosis of Chromosomal Aberrations

The diagnosis of chromosomal aberrations involves several laboratory techniques that can detect
changes in the number or structure of chromosomes in cells. These techniques include:

Karyotyping: Karyotyping is a standard technique that is the staining and visualization of

chromosomes under a microscope. This technique can detect numerical and structural
chromosomal aberrations, such as aneuploidy and translocations.

Figure 13: Normal Karyotype

“Fluorescence In Situ Hybridization (FISH)”: Fluorescent probes are used in the molecular
cytogenetic procedure known as "fluorescence in situ hybridization" (FISH) to identify particular
DNA sequences on chromosomes. This method can find structural deviations, such as deletions,
duplications, and translocations, at a higher resolution than karyotyping.
 Figure 14: Basic workflow of FISH technique

Array Comparative Genomic Hybridization (aCGH): aCGH is a high-resolution

molecular technique that compares the DNA content of a patient's sample with a control sample.
This technique can detect small copy number changes, such as deletions and duplications, across
the entire genome.
The choice of diagnostic technique depends on the type of chromosomal aberration suspected and
the level of resolution required for diagnosis. Chromosomal abnormalities must be correctly
identified in order to diagnose and treat cancer and genetic diseases.

Treatment
Some of the treatment options include:

Gene Therapy: Gene therapy is an emerging treatment option that involves correcting or
replacing the faulty genes responsible for the chromosomal aberration. This can be done by
introducing normal genes into the affected cells using viral vectors or other delivery systems. Gene
therapy is still experimental but has shown promising results in clinical trials for some genetic
disorders caused by chromosomal aberrations.

“Bone Marrow Transplantation”: Some genetic diseases, like specific forms of leukaemia or
lymphoma, brought on by chromosomal aberrations can be treated with a transplant of bone
marrow. This entails transferring good bone marrow from an appropriate donor to replace the
patient's own bone marrow. The transplanted bone marrow contains normal stem cells that can
generate healthy blood cells.

Enzyme Replacement Therapy: Enzyme replacement therapy is a treatment option for some
genetic disorders caused by chromosomal aberrations, such as Gaucher disease or Fabry disease.
This involves administering a missing or defective enzyme to the patient to compensate for the
deficient enzyme activity.
Supportive Care: Supportive care involves providing care and assistance to patients with
genetic disorders caused by chromosomal aberrations to improve their quality of life. This may
include nutritional support, counseling, and social services.

In conclusion, the treatment of chromosomal aberrations is challenging and requires a

multidisciplinary approach involving geneticists, pediatricians, hematologists, and other
specialists.

Conclusion:
In conclusion, chromosomal aberrations are genetic disorders that can be caused by a variety of
environmental and hereditary factors. They include abnormalities in chromosome structure such
as deletions, duplications, translocations, or inversions which lead to an altered number of
chromosomes. Chromosomal aberrations have been connected to many serious medical conditions
such as cancer, birth defects, and infertility so it is important for us to better understand the
underlying mechanisms responsible for them. By educating ourselves on the subject we may be
able to help combat this disease effectively and reduce its occurrence rate in our population.
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