MUTATION; ITS CAUSES, KINETICS AND

MEDICAL CONSEQUENCES

A SEMINAR PRESENTED TO THE

HAEMATOLOGY UNIT OF MEDICAL

LABORATORY SCIENCES
EVANGEL UNIVERSITY, AKAEZE, EBONYI
STATE.
BY

STUDENT SCIENTISTS

1. GODWIN GODSFAVOUR AMARACHI EU/HS/MLS/20/157

2. AMADI ADAKU FORUNATA EU/HS/MLS/20/201
3. OKECHUKWU EKEH EU/HS/MLS/20/164
4. NNAJI GOODNESS EU/HS/MLS/20/178
SUPERVISOR: DR UREME SAMUEL

DECEMBER, 2024
AIM
To understand and characterize mutation,
identify its causes and effect of change In
genetics or DNA sequence of a cell and
possible ways to prevent or fight it.
OUTLINE
 Aim
 Introduction
 Mutation and its role in DNA sequencing
 Causes of Mutation
 Kinetics
 Medical Consequences
 Management and Treatment
 Conclusion
 Recommendation
 References
INTRODUCTION
Mutation is a change in the genetic arrangement of the
DNA by removing, adding or replacing pieces of the DNA.

DNA is the information store house of all cells in both

Prokaryotic and Eukaryotic. In this DNA is contained
nucleotide which is the basic building block of nucleic acids.
The DNA sequence gives cells the information they need to
perform their functions. If part of the DNA sequence is in the
wrong place, isn't complete or is damaged, one might
experience symptoms of a genetic mutation. Therefore, any
change in nucleotide arrangement in DNA is Mutation.

Not all genetic mutations lead to genetic disorders. Some

genetic mutations don’t have any effect on health and well-
being. This is because the change in the DNA sequence
doesn’t change how the cell functions. The body also has
enzymes which helps the body protect itself from disease.
Enzymes repair a variety of genetic mutations before they
affect how a cell functions.
Some genetic mutations even have a positive effect on
humans. Changes in how cells work can sometimes improve
the proteins that cells produce and allow them adapt to
changes in the environment. An example of a positive genetic
mutation is one that can protect a person from acquiring
heart disease or diabetes, even with a history of smoking or
being overweight.

Genetic variations are important for humans to evolve, which

is the process of change over generations. A sporadic genetic
mutation occurs in one person. That person passes their
genetic mutation onto their children (hereditary), and it
continues for generations. If the mutation improves that
person’s chance of survival, or freedom from disease, then it
begins being passed through generations and spread through
the population. As the mutation passes from generation to
generation, it becomes a normal part of the human genome
and evolves from a gene variant into a normal gene.
MUTATION AND ITS ROLE IN DNA SEQUENCING

A genetic mutation is a change to a gene’s DNA sequence to

produce something different. It creates a permanent change
to that gene’s DNA sequence. It is an alteration of the
base(nucleic acid) sequence of the genome of an organism,
virus, or extra-chromosomal DNA.

Ordinarily, a mutation cannot be recognized by enzymes

once the base change is present in both DNA strands, and
thus a mutation is not ordinarily repaired. At the cellular
level, mutations can alter protein function and regulation.
Unlike DNA damages, mutations are replicated when the cell
replicates. At the level of cell populations, cells with
mutations will increase or decrease in frequency according to
the effects of the mutations on the ability of the cell to
survive and reproduce.
CAUSES OF MUTATION

Mutations have many possible causes. Some mutations seem

to happen spontaneously without any outside influence.They
can occur when mistakes are made during DNA replication
(translation synthesis) or transcription. Other mutations are
caused by environmental factors. Mutations may also result
from substitution, insertion or deletion of segments of DNA
due to mobile genetic elements.

Internal factors

1. Errors during DNA replication: Mistakes made by DNA

polymerase during replication can lead to mutations.

2. Genetic recombination: The exchange of genetic material

between chromosomes during meiosis can lead to mutations.
3. Spontaneous mutations: Random changes in DNA that
occur without any external influence.

4. Mobile genetic elements: Transposons and

retrotransposons can insert themselves into new locations in
the genome, causing mutations.

External Factors: Anything in the environment that can

cause a mutation is known as a Mutagenes.

1. Radiation: Ionizing radiation, such as X-rays, UV rays and

gamma rays, can cause DNA damage and mutations.

2. Chemical mutagens: Exposure to chemicals like mustard

gas, formaldehyde, and pesticides can cause mutations.

3. Viral infections: Certain viruses, such as HIV and HPV, can

integrate into the host genome and cause mutations.

4. Environmental toxins: Exposure to toxins like heavy

metals, pesticides, and industrial chemicals can cause
mutations.

Other factors includes:

1. Ageing: As we age, our cells ability to repair DNA damage

declines, leading to an accumulation of mutations.

2. Genetic predisposition: Some individuals may be more

prone to mutations due to their genetic makeup.
3. Epigenetic changes: Changes in gene expression that do
not involve changes to the DNA sequence itself can also lead
to mutations.

4. Mitochondrial mutations: Mutations in the mitochondrial

genome can also occur, leading to changes in energy
production and other cellular processes.

When do genetic mutations happen?

Genetic mutations occur during cell division when cells divide

and replicate. Meiosis and metosis.

How do genetic mutations happen?

When cells divide, they hand-write the body’s instruction

manual by copying the original document word for word.
There’s a lot of room for error during cell division because the
cells might substitute (replace), delete (remove) or insert
(add) letters while they’re copying. If there's an error (genetic
mutation), the genetic instruction manual for the cells may
not be readable by the cells, or may have missing parts or
unnecessary parts added. All of this can mean that the cells
can’t function as they normally should.

How do genetic mutations affect other organs?

A genetic mutation changes the information cells need to

form and function. The genes are responsible for making
proteins that tells the body what physical characteristics it
should have. There are many different diseases and
conditions caused by mutations.

Some of the thousands of genetic conditions that exist are:

1. Sickle Cell Anaemia: A point mutation in the HBB gene

causes sickle-shaped red blood cells, leading to anaemia,
pain, and increased risk of infections.

2. Cystic Fibrosis: A deletion mutation in the CFTR gene

causes respiratory, digestive, and reproductive problems.

3. Muscular Dystrophy: A frame-shift mutation in the DMD

gene causes progressive muscle weakness and degeneration.

4. Infertility: Mutations can cause infertility in both males and

female.

5. Alzheimer’s disease.

6. Some cancers.

7. Down syndrome.

8. Colour blindnes
When mutation occurs, one can experience symptoms of a
genetic condition because the cells are doing a different job
than they should. These symptoms of genetic conditions
however depends on which gene has a mutation. The signs
and symptoms you experience could include:

a) Physical characteristics like facial abnormalities, a cleft

palate, webbed fingers and toes, or short stature.
b) Birth Defects: Mutations can cause birth defects, such as
heart defects, cleft palate, and neural tube defects.
c) Problems with cognitive (intellectual) function and
developmental delays.
d) Vision or hearing loss.
e) Breathing problems.
f) Increased risk of developing cancer.

TYPES OF GENETIC MUTATIONS

It generally starts from DNA arrangement;

1. DNA point mutation.

2. Insertion mutation(frame-shift mutation)
3. X- Linked mutation.
Point Mutation is the alteration of single base pairs.
Frame-Shift Mutation is the insertion or deletion of
one or more base pairs of the DNA molecule. These
 mutations change the entire “reading frame” of the
DNA/amino acid sequence and typically lead to a
premature stop codon downstream of the mutation.
X-Linked Mutation Some chromosomal disorder
can be due to structural disorder or numerical disorder.

Structural Disorder manifests a kind of deletion or

insertion in the DNA while Numerical Disorder manifests
in form of extra chromosome in the individual. E.g:

XXX -Though female, but have male characteristics and

usually limited fertility.

XXY – Though male, but usually have female

characteristics, such as low voice, small gonads,
increased breast.

XYY -Though male, but with additional features that may

result in anti-social behaviour.

Types of genetic mutations based on DNA segment:

1. Monogenic: mutation of one gene. They are also called

SINGLE- GENE mutation because the nucleotide changes occur
within a segment of DNA.
2. Multiple Gene Mutation also known as Polygene Mutation i.e
mutation involving multiple genes.
3. MULTIFACTORIAL MUTATION are those mutation arising from
other factors apart from DNA but can affect somatic genes leading
to changes that can be seen in members of the same family but
such changes are not transmittable.
NON SENSE MUTATON are mutation that produce ineffective proteins
or a mutation that produce stop codon that leads to Pre-mature
chain termination in the DNA. In many nonsense mutation, the DNA
sequence is usually shorter resulting in an unfinished product.

BASE SUBSTITUTION is a mutation that results from replacement of

one pyrimidine base with another. For instance, A can be replaced
with T. In this case, if the replaced base code for the same amino
acid, it is called a MisSense mutation. In either of this mutation can
occur in addition or deletion.

ADDITION MUTATION is one that adds a nucleotide in the growing

chain of DNA.

DELETION MUTATION occurs when a nucleotide is deleted from a

DNA segment resulting also in a frameshift. Deletion or Addition
Mutation usually changes the reading frame, resulting in a different
AA arrangement either downstream of the mutation.

Types of genetic mutations based on where they form

include:

1. Germ-line mutation: A change in a gene that occurs in a

parent’s reproductive cells (egg or sperm) that affects the
genetic makeup of their child (hereditary).
2. Somatic mutation: A change in a gene that occurs after
conception in the developing embryo that may become a
baby. These occur in all cells in the developing body —
except the sperm and egg. Somatic mutations can’t pass
from parents to their children (hereditary) because traits
are passed only from the sperm and egg.
Patterns through which mutation is passed
These are mutations that follows Mendelian Law of
Inheritance and those that don’t.
Mutation following mendelian law includes:

 Autosomal dominant: Only one parent needs to pass the

genetic mutation onto their child. E.g Marfan
syndrome
 Autosomal recessive: Both parents need to pass the
same genetic mutation onto their child. E.g Sickle cell
disease
 X-linked dominant: Babies assigned male or female have
an X chromosome. Only one mutation on the X
chromosome needs to pass from one parent to the
child for the child to inherit the mutation. Fragile X
syndrome
 X-linked recessive: If only dad has the mutation, there’s
100% that female offspring will be carriers and no male
offspring will be affected. If only mom had the
mutation, there’s a 50% chance that female offspring
will be carriers and a 50% chance male offspring will
have the condition. If both parents have the mutation,
50% of male offspring will have the condition and 100%
of female offspring will have the mutation.e.g Color
blindness
 X-linked: Babies assigned male or female have an X
chromosome. Mutations on the X chromosome can
pass in a dominant or recessive pattern, but not every
pattern is clear on how the child acquired the mutation
from their parents. Thrombocytopenia
  Y-linked: Only babies assigned male at birth have a Y
chromosome and can inherit this type. E.gWebbed toes

Mutation that doesn’t follow Mendelian Law of Inheritance

includes;
 Mitochondrial Disorder
 Germline disorder-such as germline mosaicism.

KINETICS OF MUTATION
The kinetics of mutation refers to the rates and mechanisms
by which genetic mutations occur. Here’s an overview:

1. Point mutations (substitutions, insertions, deletions)

2. Chromosomal mutations (translocations, duplications,

deletions)

3. Epigenetic mutations (changes in gene expression without

DNA sequence changes)

Mutation Rates

1. Spontaneous mutations: occur naturally, estimated 1-2 per

10^6 cell divisions

2. Induced mutations: result from environmental factors

(radiation, chemicals), varying rates

Factors Influencing Mutation Rates

1. DNA replication fidelity

2. Repair mechanisms (proofreading, mismatch repair)

3. Environmental stressors (radiation, chemicals)

4. Genetic predisposition (e.g., inherited mutations)

5. Epigenetic regulation

Kinetic Models

1. Neutral theory: mutations accumulate neutrally, without

selection

2. Nearly neutral theory: slightly deleterious mutations can

accumulate

3. Mutation-selection balance: balance between mutation

and selection pressures.

1. Mutation rate (μ) = number of mutations / number of cell

divisions

2. Genetic drift (Δp) = change in allele frequency / generation

Important Concepts

1. Mutation spectrum (types and frequencies)

2. Mutation hotspots (regions prone to mutations)

3. Genetic hitchhiking (neutral mutations linked to beneficial
ones)

Understanding mutation kinetics is crucial in:

1. Cancer research

2. Genetic disease diagnosis

3. Evolutionary studies

4. Synthetic biology
MEDICAL CONSEQUENCES OF MUTATION

Mutations can have significant medical consequences,

depending on the type, location, and severity of the
mutation. Here are some possible medical consequences of
mutations:

Consequences of Mutations

1. Genetic variation

2. Evolution

3. Disease susceptibility

4. Cancer development

Increased Risk of Cancer_

1. *BRCA1 and BRCA2*: Mutations in these genes increase

the risk of breast, ovarian, and other cancers.

2. *TP53*: Mutations in this gene increase the risk of various

cancers, including breast, lung, and colon cancer.

Neurological Disorders
1. Huntington's Disease: An expansion mutation in the HTT
gene causes progressive damage to the brain, leading to
cognitive, motor, and psychiatric problems.

2. Amyotrophic Lateral Sclerosis (ALS): Mutations in the SOD1

gene cause progressive damage to motor neurons, leading to
muscle weakness and paralysis.

Metabolic Disorders

1. Phenylketonuria (PKU): A point mutation in the PAH gene

causes an inability to metabolize phenylalanine, leading to
intellectual disability and other complications.

2. G6PD Deficiency: A point mutation in the G6PD gene

causes an inability to protect red blood cells from oxidative
damage, leading to anemia and other complications.

Immunological Disorders

1. Severe Combined Immunodeficiency (SCID): Mutations in

the ADA or IL2RG genes cause impaired immune function,
leading to recurrent infections and other complications.

2. Autoimmune Disorders: Mutations in genes involved in

immune regulation, such as CTLA-4, can increase the risk of
autoimmune disorders like rheumatoid arthritis and lupus
MANAGEMENT AND MONITORING OF TREATMENT

Genetic testing and counseling can help identify individuals

at risk and provide guidance on prevention, diagnosis, and
treatment.

Mutation however can be identified through genetic test.

This requires a sample of patients blood, skin, hair, amniotic
fluid or tissues to identify changes in the genes,
chromosomes or proteins. Genetic testing can locate mutated
genes or chromosomes that cause genetic conditions. These
tests also provides information on risk of having a child with a
genetic condition.

Here are steps to prevent some genetic mutations:

I. Not smoking.
II. Wearing sunscreen when out in the sun.
III. Avoiding chemical exposure (carcinogens) or exposure to
radiation (X-ray exposure).
IV. Eating a healthy, balanced diet and avoiding processed
foods.

Treatment methods includes:

I. Gene therapy: A technique that aims to fix or replace a

faulty gene with a healthy one. It can be used to treat
cancer, cystic fibrosis, and heart disease.
II. Targeted therapies: A cancer treatment that targets the
genetic mutations found in a tumor.
CONCLUSION
While some genetic mutations can lead to genetic conditions,
most mutations don’t cause symptoms in humans and one
can inherit the genetic condition from parents if it’s germ cell
DNA in the sperm or egg. It’s difficult to prevent mutations
from happening, especially as genetic mutations can occur
randomly, some without being present in the family history.
REFERENCES

National Institutes of Health (NIH)_

1. National Human Genome Research Institute. (2022). Genetic Disorders.

2. National Cancer Institute. (2022). Genetic Changes and Cancer.

_Scientific Journals_

1. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular
Biology of the Cell. 5th edition.

2. Griffiths, A. J. F., Wessler, S. R., Lewontin, R. C., & Gelbart, W. M. (2008). An Introduction to
Genetic Analysis. 9th edition

Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. (2006).
DNA repair and mutagenesis. American Society for Microbiology.

Kimura, M. (1968). Evolutionary rate at the molecular level. Nature, 217(5129), 624-626.

Kondrashov, A. S. (2003). Direct estimates of human per nucleotide mutation rates at 20 loci
causing Mendelian diseases. Human Mutation, 21(1), 12-27.

Kunkel, T. A. (2004). DNA replication fidelity. Journal of Biological Chemistry, 279(17), 16895-
16898.

Ohta, T. (1973). Slightly deleterious mutant substitutions in evolution. Nature, 246(5434), 96-
98.

2.Radiation_:

- Hall, E. J., & Giaccia, A. J. (2012). Radiobiology for the radiologist. Lippincott Williams &
Wilkins.

3.Viral infections_:

- Knipe, D. M., & Howley, P. M. (2013). Fields virology. Lippincott Williams & Wilkins.
_Online Resources_

1. Genetics Home Reference. (2022). Help Me Understand Genetics.

2. MedlinePlus. (2022). Genetic Disorders.

3. http-cleavelandclinic.org