Mutation
Human Genetic
Mutations
MUTATIONS
Changes in DNA that
affect genetic information
• Changes in the nucleotide
sequence of DNA
• May occur in somatic
cells (aren’t passed to
offspring)
• May occur in gametes
(eggs & sperm) and be
passed to offspring
Mutation
Mutations are changes in the genetic sequence, and they are
the main cause of diversity among organisms. Mutation also
refers to a change that affects the nucleic acids. In cellular
organisms, these nucleic acids are the building blocks of
DNA, and in viruses they are the building blocks of either
DNA or RNA. One way to think of DNA and RNA is that they
are substances that carry the long-term memory of the
information required for an organism's reproduction.
a mutation is a permanent alteration of
the nucleotide sequence of
the genome of an organism, virus, or
extrachromosomal DNA or other
genetic elements
Are Mutations Helpful or Harmful?
• Mutations happen regularly
• Almost all mutations are
neutral
• Chemicals & UV radiation
cause mutations
• Many mutations are
repaired by enzymes
• Some type of skin cancers
and leukemia result from
somatic mutations
• Some mutations may
improve an organism’s
survival (beneficial)
TYPES OF
MUTATION
2 Main Types of Mutations
1. Gene Mutation
A. Point Mutation
B. Frameshift Mutation
2. Chromosomal Mutation
2 Main Types of Mutations
1. Gene
Mutation
Gene Mutations
• Change in the nucleotide
sequence of a gene
• May only involve a single
nucleotide
• May be due to copying
errors, chemicals,
viruses, etc.
Gene Mutations
• Small scale: one gene is
affected
• Any change to the DNA
sequence of a gene:
Nucleotides/Bases may be
added, missing, or changed
Gene Mutations: 2 Types
Gene Mutations
Point Mutations –
changes in one or
a few nucleotides
• Change of a single
nucleotide
• Includes the deletion,
insertion, or
substitution of ONE
nucleotide in a gene
• One base (A, T, C, or G) is substituted for
another
• 3 Possible Consequences:
nonsense mutations: code for a stop, which
can translate the protein
missense mutations: code for a different
amino acid
silent mutations: code for the same amino
acid
Substitution
A substitution is a mutation that exchanges one base for
another (i.e., a change in a single "chemical letter" such as
switching an A to a G). Such a substitution could:
change a codon to one that encodes a different amino acid
and cause a small change in the protein produced. For
example, sickle cell anemia is caused by a substitution in the
beta-hemoglobin gene, which alters a single amino acid in the
protein produced.
Substitution
THE FAT CAT ATE THE RAT
THE FAT HAT ATE THE RAT
Insertion
Insertions are mutations in which
extra base pairs are inserted into a
new place in the DNA
Insertion
THE FAT CAT ATE THE RAT
THE FAT CAT XLW ATE THE RAT
Deletion
Deletions are mutations in which a
section of DNA is lost, or deleted
Deletion
THE FAT CAT ATE THE RAT
THE FAT ATE THE RAT
Normal Red Blood Cell Sickle Red Blood Cell
• Red blood cells shaped like a disc • Red blood cells form an abnormal
• Hemoglobin (protien) carries crescent shape
oxygen to all parts of the body • Hemoglobin (protein) is abnormally
shaped
• don't move easily through your
blood vessels
• form clumps and get stuck in the
blood vessels
Point Mutation
• Sickle Cell disease
is the result of one
nucleotide
substitution
• Occurs in the
hemoglobin gene
Gene Mutations
Frameshift Mutations –
shifts the reading frame
of the genetic message
so that the protein may
not be able to perform its
function.
• Inserting or deleting
one or more nucleotides
• Changes the “reading
frame” like changing a
sentence
• Proteins built
incorrectly
• One or more bases (A, T, C,
or G) are added or deleted
• Caused by:
–Insertion: adding a base
–Deletion: removing a base
Insertion
THE FAT CAT ATE THE RAT
THE FAT HCA TAT ETH ERA T
H
Deletion
THE FAT CAT ATE THE RAT
H
TEF ATC ATA TET GER AT
Frameshift Mutation
• Original:
–The fat cat ate the wee
rat.
• Frame Shift (“a” added):
– The fat caa tet hew
eer at.
Amino Acid Sequence
Changed
Example: Cystic Fibrosis (CF)
• What is it?
– Autosomal, recessive
disorder
• Symptoms
– Thick mucus in the lungs and digestive
track
– Constant lung infections and impaired
digestion
Cystic Fibrosis (CF)
• Who gets it?
– Anyone
– Most common in Caucasians
• Prevalence
– 1 in ~3,000 Americans has CF
– 1 in 23 white Americans carries the
mutant allele!
Cause of Cystic Fibrosis (CF)
• The “CFTR” gene is mutated
– 3 base pairs are deleted
• Mutant protein is missing an amino acid
and cannot fold correctly
vs
Normal CFTR protein:
Ion channel in cell membrane
Gene Mutations
• KEY IDEA: A mutated gene will make a
mutated protein
• Mutant proteins are trouble!
–They do not go where they are
supposed to go
–They do not do what
they are supposed to do
