MUTAT ION &
Genetic Disorder
Review: The Central Dogma
DNA
Transcription
mRNA
Translation
Protein
Trait
Lobster claw
Progeria
AKA as “ostrich foot,” ectrodactyly is all too
real. Caused by a mutation in chromosomes causes accelerated aging in children
10, 7, 3, or 2, this x-linked condition results
tend to have aged-looking skin, bone
in “split“ hands and feet.
and heart problems, and a loss of the
There is a 50% chance of an individual fat beneath the skin.
passing a mutated gene to a child, regardless
of the gender of the child.
"Have you ever wondered why some
people inherit diseases while others
don't? What happens if even one
letter in our DNA changes?"
"If DNA is the instruction
manual, what happens
when there is a typo in the
instructions?"
Learning Objectives:
▻ Describe the different types of DNA
mutations
▻ Explain how mutations affect gene
expression and protein function
▻ Relate DNA mutations to genetic
disorders.
WHAT IS A GENETIC
MUTATION?
o A genetic mutation is a change
that occurs in our DNA code
(sequence of nucleotides).
o A mutation is a permanent change
in the DNA sequence.
• Mutations may
• change one
nucleotide
• add nucleotides
• remove
nucleotides
• rearrange DNA
• Mutations can be
• beneficial
• harmful
• neutral
WHAT CAUSES
MUTATIONS?
Errors in DNA replication during cell division.
Exposure to mutagens (radioactive substances, x-
rays, ultraviolet radiation and certain chemicals).
Viral infections and other infectious agents.
Different types of genetic mutations
Germline mutation: a 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).
Somatic mutation: A change in a gene that occurs after
conception in the developing embryo that may become a baby.
Somatic mutations can’t pass from parents to their children
(hereditary) because traits are passed only from the sperm and
egg.
WHAT CAN HAPPEN?
Some mutations do not cause any noticeable
changes, while others can lead to genetic disorders
or diseases.
Mutations can even give an organism an advantage in
its environment, leading to new traits or abilities
(species evolution).
2 Category of mutation
Small scale ( Gene) mutations- these affect a single
gene or small number of nucleotide bases.
Large-Scale (Chromosomal) mutations- These affect
the structure or number of whole chromosomes, often
causing severe developmental conditions
TYPES OF MUTATIONS
[Link]
One base is replaced
[Link]
extra base(s) is added
[Link]
Base (s) removed
For example, a G
[Link] (guanine) might be
Reading frame changes because of insertion/deletion swapped for a C
(cytosine).
When do mutations
happen?
Occurs during cell division
Mitosis: the process of making new cells
for your body
Meiosis: The process of making egg and sperm cells
for the next generation..
Point Mutation (Substitution) Mutation
occurs when one nucleotide (DNA base) is Example
replaced by another nucleotide.
Original DNA
DNA: TAC GAA TCG
substitution mutations do not change the
Mutated DNA
number of nucleotides in the DNA
sequence. DNA: TAC GTA TCG
Substitution Mutation
Key Point:
▻ Only one nucleotide changes.
▻ The reading frame remains the same.
▻ The effect depends on which codon is altered.
How Substitution Mutations Affect
Gene Expression
Normal Gene Expression With a Substitution Mutation
DNA DNA (one base changed)
Transcription Transcription
mRNA Mutated mRNA
Translation Translation
Functional Protein Protein may be:
•Normal
•Slightly altered
•Nonfunctional
Types of Substitution
Mutations
a. Silent Mutation
b. Missense Mutation
c. Nonsense Mutation
A. Silent Mutation
The DNA sequence changes but the
amino acid remains the same.
Because several codons can code for the
same amino acid (genetic code
redundancy), the protein is unchanged.
Result:
Protein function is usually unaffected.
Example: Silent Mutation
DNA:
Original Mutated
AAA AAG
mRNA
Original Mutated
UUU UUC
Amino Acid
Both codons code for Phenylalanine.
Result
Protein remains unchanged.
B. Missense Mutation
▪ The substitution changes one amino
acid in the protein.
▪ The new amino acid may alter the
protein's structure or function.
Result:
Protein may function normally, less
efficiently, or not at all.
Example: Sickle Cell Anemia
DNA:
Original Mutated
CTT CAT
Amino Acid
Glutamic Acid Valine
Result
The altered hemoglobin molecules stick together when
oxygen levels are low, causing red blood cells to
become rigid and sickle-shaped.
Example: Sickle Cell Anemia
Symptoms
▪ Anemia
▪ Pain crises
▪ Fatigue
▪ Increased risk of infection
Key Point
Only one amino acid changes, but it significantly affects the
protein's function.
C. Nonsense Mutation
▪ The substitution changes a codon into
a stop codon.
▪ Translation stops prematurely.
Result:
▪ A shortened (truncated) protein is produced.
▪ The protein is usually nonfunctional.
Example: Beta-thalassemia
Example:
Normal mRNA Mutated mRNA
UAU UAA
(Tyrosine) STOP
Translation stops too early.
Result
▪ Shortened beta-globin protein
▪ Reduced or absent hemoglobin production
▪ Anemia
Example of diseases
a. Sickle cell anemia
b. Achondroplasia
c. Huntington's Disease
d. Cystic Fibrosis
e. Albinism
f. Marfan Syndrome
SUMMARY
Type DNA Change Protein Effect Example
One base No amino acid Usually no
Silent
changes change disorder
One base One amino acid Sickle cell
Missense
changes changes disease
One base Premature stop Beta-thalassemia
Nonsense
changes codon (some cases)
Insertion Mutation
▪ occurs when one or more
nucleotides (DNA bases) are
added to the DNA sequence.
▪ increase the length of the
DNA sequence. Their effect
depends on how many
nucleotides are inserted.
Insertion Mutation Example
Original DNA Sequence Mutated DNA Sequence
DNA DNA
ATG CCA GTA TTC ATG ACC AGT ATT C
mRNA mRNA
AUG GGU CAU AAG AUG UGG UCA UAA G
Translation Translation
Met., Gly., His., Lys. Met., Trp., Ser., Stop
Because the insertion changed the reading frame, a premature stop
codon (UAA) appears, producing a shortened protein.
Type of Insertion mutation
1. In-Frame Insertion Result:
If three nucleotides are o One extra amino acid is
inserted, the reading frame added.
is maintained.
o The rest of the protein
Original: remains unchanged.
ATG CCA GTT
o Protein function may be
Insert GAA: unaffected or only
ATG GAA CCA GTT slightly altered.
Type of Insertion mutation
2. Frameshift Insertion Result:
If one or two o Every codon after the
nucleotides are inserted, insertion changes.
the reading frame shifts. o Different amino acids are
produced.
Original: o A premature stop codon
ATG CCA GTT AAC may appear.
Insert: o The protein is usually
ATG ACC AGT TAA C nonfunctional.
Effects on Protein Function
Insertion mutations can result in:
No significant effect – if the inserted amino acid does
not affect protein function.
Altered protein function – if the insertion changes the
protein's shape or activity.
Loss of protein function – if a frameshift introduces a
premature stop codon, producing an incomplete protein.
Example of Insertion Diseases
a. Tay-sachs Disease
b. Fragile X syndrome
c. Charcot-Marie (Tooth Disease)
d. BRCA1-related (Breast Cancer)
e. Spinocerebellar (Ataxia)
f. Myotonic Dystrophy
Deletion Mutation
▪ occurs when one or more nucleotides (DNA
bases) are removed from a DNA sequence.
Normal Gene Expression After Deletion
DNA DNA
ATG CCA GTT AAC ATG CAG TTA AC...
mRNA mRNA
AUG GGU CAA UUG AUG GUC UUA UG...
Protein Protein
Met, Gly, Gln, Leu Methionine – Val. – Phe – ...
Because one nucleotide was deleted, the codons changed from the point of mutation onward,
producing a different amino acid sequence.
Types of Deletion mutation
1. In-Frame Deletion
occurs when three or a
multiple of three Effect:
nucleotides are removed.
The effect depends on whether
the missing amino acid is
Original:
important for the protein's
ATG CCA GTT AAC structure or function.
Mutated DNA
ATG GTT AAC
Type of Deletion mutation
2. Frameshift Deletion
occurs when one or two Effect
nucleotides (or any number • Reading frame changes.
not divisible by three) are • Every codon after the
removed. deletion changes.
• A premature stop codon
Original: often appears.
ATG CCA GTT AAC • The protein is usually
shortened and
Deletion:
nonfunctional.
ATG CAG TTA AC...
Effects on Protein Function
Deletion mutations may result in:
No Significant Effect
✓ If the deleted amino acid is not essential to the
protein.
Altered Protein Function
✓ The protein still forms but works less efficiently.
Loss of Protein Function
✓ Frameshift mutations often produce a severely
altered or incomplete protein.
Example of Deletion Diseases
a. Cystic Fibrosis (F508)
b. Duchenne Muscular Dystrophy
c. Prader-Willi Syndrome
d. Angelman Syndrome
e. Alpha thalassemia
f. DiGeorge Syndrome
Frameshift Mutation
▪ mutation caused by the insertion or deletion of
nucleotides in a DNA sequence in a number
that is not a multiple of three, which disrupts
the reading frame of codons.
How It Works
DNA is read in triplets
called codons, each coding for a
specific amino acid. If the number
of nucleotides shifts, every codon
downstream of the mutation
changes.
Frameshift Mutation
Normal sequence:
ATG | CAT | GCA | TGA
Met – Val – Arg – Thr Two Types:
After inserting one nucleotide (A) at
Insertion — one or more
position 4th :
nucleotides are added
ATG | ACA | TGC | ATG | A...
Met – Cys – Thr – Met – ... Deletion — one or more
nucleotides are removed
Every codon after the insertion is
scrambled.
Consequences
Frameshift mutations are generally severe because
they:
• Alter every amino acid after the mutation point
• Often introduce a premature stop codon,
truncating the protein
• Produce a nonfunctional or drastically altered
protein
• Can cause loss-of-function diseases
Example of Diseases
a. Tay-Sachs Disease
b. Duchenne Muscular Dystrophy
c. Lynch Syndrome
d. Crohn’s Disease
e. Beta thalassemia
f. Li-Fraumeni Syndrome
Quick Summary
Mutation Type Key Feature Severity
Substitution Single base swap Mild to severe
Deletion Nucleotide(s) removed Moderate to severe
Insertion Nucleotide(s) added Moderate to severe
Frameshift Reading frame disrupted Usually severe
Thank you for
Listening