Mutations

What Are Mutations?

• Changes in the nucleotide

sequence of DNA
• May occur in somatic cells(body
cells)
• May occur in gametes (eggs &
sperm) and be passed to
offspring
 Are Mutations Helpful or
Harmful?

1. Mutations happen all the time

2. Almost all mutations are neutral
3. Chemicals & UV radiation cause
mutations
4. Many mutations are repaired by
enzymes(DNA polymerase)
 Consequence of Mutations
• Most mutations are minor
• Many are harmful
• Some are lethal
• A few may be helpful
 Significance of Mutations
• Most are neutral
• Eye color
• Birth marks
• Some are harmful
• Sickle Cell Anemia
• Down Syndrome
• Some are beneficial
• Sickle Cell Anemia to Malaria
• Immunity to HIV
 What Causes Mutations?

• There are two ways in which DNA

can become mutated:
– Mutations can be inherited.
• Parent to child
– Mutations can be acquired.
• Environmental damage
• Mistakes when DNA is copied
 Are Mutations Helpful
or Harmful?

• Some type of skin cancers and

leukemia result from somatic
mutations
• Some mutations may improve an
organism’s survival (beneficial)
 TYPES OF MUTATIONS
1.Chromosome mutations
• Changes in chromosome
structure
• Changes in chromosome
number
2. Gene mutations
• Relatively small changes in
DNA structure
• Occur within ONE particular
gene
9
 Chromosome Mutations

• May Involve:
– Changing the
structure of a
chromosome
– The loss or
gain of part of
a chromosome
Chromosome Mutations

• Five types exist:

– Deletion
– Inversion
– Translocation
– Nondisjunction
– Duplication
 Deletion
• Due to breakage
• A piece of a
chromosome is lost
 Inversion

• Chromosome segment
breaks off
• Segment flips around
backwards
• Segment reattaches
 Duplication
• Occurs when a
gene sequence is
repeated
 Translocation
• Involves two
chromosomes that
aren’t homologous
• Part of one
chromosome is
transferred to
another chromosomes
Translocation
 Nondisjunction
• Failure of chromosomes to separate
during meiosis
• Causes gamete to have too many or
too few chromosomes
• Disorders:
– Down Syndrome – three 21st chromosomes
– Turner Syndrome – single X chromosome
– Klinefelter’s Syndrome – XXY chromosomes
Chromosome Mutation
Animation
 Gene Mutations
Changes in a single gene
• Takes place during DNA
replication
• Can involve one or more
nucleotides (bases)
• May be due to copying
errors,
• chemicals,
• viruses, etc.
Types of Gene Mutations
1. Point mutations
• A substitution one
nitrogen base in a DNA
sequence
Effects of this change
a. Missense
b. Nonsense
c. Silent
 Gene Mutations

• Point Mutations – changes in one or a

few nucleotides
– Substitution
• THE FAT CAT ATE THE
RAT
• THE FAT HAT ATE THE
RAT
Missense
A type of point mutation
that results in a change in
a single mutation.
Protein is changed
EXAMPLE: sickle cell
anemia
Types of Gene Mutations
1. Point - Missense
• One base is replaced by a different
one resulting in a change an amino
acid of a protein which DOES change
the protein!!!!!
– Normal DNA: TGA TCT ACT
– mRNA: ACU AGA UGA
amino acid: (arginine)

Substitution= DNA: TGA TCC ACT

– mRNA: ACU AGG UGA
amino acid: (arginine)
or
Substitution= DNA: TGA TTT ACT
– mRNA: ACU AAA UGA
amino acid: (lysine)
 Types of Gene Mutations
Point mutation.Substitution
– Sickle Cell Anemia
– Normal-
DNA: TAG CTT ATT
mRNA: AUC GAA UAA

– Sickle Cell-
DNA: TAG CAT ATT
mRNA: AUC GUA UAA

Change in one amino acid

– Glutamic acid is replaced
by Valine
 Point Missense Mutation
• Sickle Cell disease
is the result of one
nucleotide
substitution
• Occurs in the
hemoglobin gene
• One amino acid
change causes the
protein to not fold
correctly.
• This is what happens in sickle cell anemia. The 17th
nucleotide of the gene for the beta chain of
hemoglobin is changed from an 'a' to a 't'. This changes
the codon from 'gag' to 'gtg' resulting in the 6th amino
acid of the chain being changed from glutamic acid to
valine. This apparently trivial alteration to the beta
globin gene alters the quaternary structure of
hemoglobin, which has a profound influence on the
physiology and wellbeing of the individual
Nonsense mutations
A type of Point mutations that
create a premature stop codon.
The protein is too short.
Causes Cystic Fiberosis
• Nonsense mutations occur in between
15% to 30% of all inherited diseases
including cystic fibrosis, hemophilia,
retinitis pigmentosa and duchenne
muscular dystrophy.
• Cystic fibrosis is a severe, genetically determined
disease that involves both the lungs and the
gastrointestinal tract. It occurs in about one in every
two thousand births among white children and at a
far lower rate in asian and black children. There are
now more than 500 different mutations known to
cause the disease. These mutations occur in a huge
gene on chromosome 7 that encodes a protein of
1480 amino acids called the cystic fibrosis
transmembrane conductance regulator (CFTR).
 The Cause of Cystic
Fibrosis

CFTR
gene

The most common Normal CFTR is a The cells in the

allele that causes chloride ion channel person’s airways are
cystic fibrosis is in cell membranes. unable to transport
missing 3 DNA bases. Abnormal CFTR chloride ions. As a
As a result, the amino cannot be result, the airways
acid phenylalanine is transported to the become clogged with a
missing from the cell membrane. thick mucus.
CFTR protein.
 Silent Mutation
• A type of point mutation
that does not change the
amino acid.
 2. Frameshift Mutations
Frameshifts occur when a base
is inserted or deleted from
the DNA sequence
– Insertions
- Deletions

- This causes the frames being

read to bond the incorrect
amino acids
 Frameshift Mutation

• Inserting or deleting
one or more
nucleotides
• Changes the “reading
frame” like changing a
sentence
• Proteins built
incorrectly
 Gene Mutations
• Frameshift Mutations – shifts the reading
frame of the genetic message so that the
protein may not be able to perform its
function.
– Insertion
• THE FAT CAT ATE THE RAT
• THE FAT HCA TAT ETH ERA
T

– Deletion
• THE FAT CAT ATE THE RAT
H
• TEF ATC ATA TET GER AT

H
Insertion
One base is
added
to the DNA
segment Insertion
Causes a
frameshift
Insertion mutations
• Causes Fragile X chromosome
• Males receive this X from their mom
and causes mental retardation.
• C and G repeat over and over.
Examples – Huntington’s, some
Parkinson’s, and Lou Gehrig’s
disease
• In Huntingtons disease, the repeated
trinucleotide is 'cag'. This adds a string of
glutamines to the Huntington protein.
The abnormal protein produced interferes
with synaptic transmission in parts of the
brain leading to involuntary movements
and loss of motor control
• Fragile X syndrome is caused when a locus
on the X chromosome contains a stretch of
nucleotides in which the triplet 'cag' is
repeated (as many as 400 times). This
causes a constriction in the x chromosome
making it quite fragile. Males who inherit
this X chromosome are mentally retarded.
Females are only mildly affected.
Deletion
– One base is omitted
from DNA segment
– Causes a frameshift

Deletion
 Examples of insertion and deletions -
FRAMESHIFTS
• The sun was hot but the old man did not get his hat.

• The unw ash otb utt tho ldm and idn otg eth ish at

• By deleting the s in sun the whole protein is made wrong

• The ssu nwa sho tbu tth eol dma ndid dno tge thi sha t

• By inserting an extra s, the protein would be read

incorrectly.
• Frameshift mutations may be beneficial, deleterious,
or lethal. For example, induction of frameshift
mutation has been used to make certain bacteria
capable of producing nylonase, an enzyme that can
degrade nylon.
• Frameshift mutation has also been one of the
possible causes of albinism. A shift in the reading
frame can lead to formation of stop codon, hence,
early terminating protein translation. An early
termination of any of the enzymes necessary for the
production of melanin can result in albinism.
• Tay Sachs disease is an example of a
disease caused by frameshift mutation.
The disease is caused by various
mutations, including frameshift
mutations, on chromosome 15 in the
HEXA gene that codes for the alpha-
subunit of the lysosomal enzyme beta-N-
acetylhexosaminidase A.
 Frameshift Mutation
• Original:
– The fat cat ate the wee
rat.
• Frame Shift (“a” added):
– The fat caa tet hew
eer at.
 Gene Mutations
Point Mutations – changes in one or a few
nucleotides
– Substitution
• THE FAT CAT ATE THE RAT
• THE FAT HAT ATE THE RAT
– Insertion
• THE FAT CAT ATE THE RAT
• THE FAT CAT XLW ATE THE
RAT
– Deletion
• THE FAT CAT ATE THE RAT
• THE FAT ATE THE RAT
Types of Gene Mutations

Frame shift mutations:

– Caused by the insertion or
deletion of
a nitrogen base in the DNA
sequence
– Shifts the “reading frame” of
the
genetic message
– Affects every amino acid that
follows
the point of insertion or
deletion
– Can alter a protein so that it
cannot perform its normal
function
Amino Acid Sequence
Changed
Types of Gene Mutations
Example of deletion mutations:
– Tay Sachs disease:
• A genetic abnormality caused by large
amounts of lipids built up on neurons in
the brain
• Leads to paralysis
– Cystic Fibrosis:
• Deletion- Three nucleotides or
Normal- one codon TAG
DNA: omitted.TAA AAA CCT CAC
mRNA: AUC AUU UUU GGA GUG
Cystic DNA: TAG TAA CCT CAC

Fibrosis- mRNA: AUC AUU GGA GUG

 The Cause of Cystic
Fibrosis

CFTR
gene

The most common Normal CFTR is a The cells in the

allele that causes chloride ion channel person’s airways are
cystic fibrosis is in cell membranes. unable to transport
missing 3 DNA bases. Abnormal CFTR chloride ions. As a
As a result, the amino cannot be result, the airways
acid phenylalanine is transported to the become clogged with a
missing from the cell membrane. thick mucus.
CFTR protein.
EFFECTS OF MUTATIONS

54
FYI
Normal Male

2n = 46 56
Normal Female

2n = 46 57
 Male, Trisomy 21 (Down’s)

Down’s
syndrome –
(Trisomy 21)
47
chromosomes,
extra
chromosome
at pair #21

2n = 47 58
 Male, Trisomy 21 (Down’s)

Down’s
syndrome –
(Trisomy 21)
47
chromosomes,
extra
chromosome
at pair #21

2n = 47 59
Female Down’s Syndrome

2n = 47 60
 Edwards Syndrome

-Second
most
common
trisomy
after
Down’s
Syndrome,
a trisomy of
chromosom
e 18
2n = 45
61
Edwards Syndrome

2n = 45
62
 Klinefelter’s Syndrome
Klinefelter’s
syndrome – 47
chromosomes, extra
X chromosomes
(XXY)
Boys affected – low
testosterone levels,
underdeveloped
muscles, sparse
facial hair

2n = 47 63
 Klinefelter’s Syndrome
Klinefelter’s
syndrome – 47
chromosomes, extra
X chromosomes
(XXY)
Boys affected – low
testosterone levels,
underdeveloped
muscles, sparse
facial hair

2n = 47 64
Turner’s Syndrome

2n = 45
65
Turner’s Syndrome

2n = 45
66
Turner’s Syndrome

2n = 45
67
 CHROMOSOMAL MUTATION
Patau syndrome,
•Trisomy 13 The extra copy of chromosome 13 in Patau syndrome
causes severe neurological and heart defects that make it difficult fo
infants to survive.
•Patau appears to affect females more than males, most likely becaus
male fetuses do not survive until birth.
•Extra fingers or toes (polydactyly)Deformed feet, known as rocker-
bottom feet
•Facial defects such as small eyes (microphthalmia), absent or
malformed nose, cleft lip and/or cleft palate
•Heart defects (80 percent of individuals)
•Kidney defects
 CHROMOSOMAL MUTATION
Patau syndrome.
 Chromosomal Mutations

Results in changes in whole chromosomes

Can cause changes in the number of chromosomes
– Can be neutral, have a
minor affect
or be lethal
– Examples:
• Trisomy 21 (Down Syndrome)
• Klinefelter Syndrome
• Trisomy 13
• Turner’s Syndrome
 Chromosomal Mutations

Can cause changes within the chromosomes

– Location
of genes
– Number
of genes
– These
letters
represent
genes
 Chromosomal Mutations

Types of Chromosomal Mutations:

– A deletion involves the loss of all or
part of a chromosome
– A duplication occurs when a segment of
a chromosome is repeated
– An inversion happens when part of a
chromosome becomes reversed
– A translocation occurs when part of one
chromosome breaks off and attaches to
another, non-homologous chromosome
Deletion

Duplication

Inversion

Translocation
Mutation Examples
Missing parts:
Mutation Examples
Color Variation:

 The rare black jaguar!

(A gene mutation overproduces
melanin in the fur.)
 Mutation Examples
Muscle bound:
Belgian
Blue bull
showing
double
muscling –
no steriods,
its a gene
mutation for
muscle growth
that caused this
to happen.

A baby Superman, born in Berlin with bulging arm

and leg muscles. Not yet 5, he has muscles twice the
size of other kids his age and half their body fat. DNA
testing showed why: The boy has a genetic mutation
that boosts muscle growth.
 Mutation Examples
• Phenotypic expression of aniridia with PAX6
gene mutation.
 Mutation Examples
Extra parts:
 Mutation Examples
Extra parts:
 Mutation Examples
Extra parts:
 Mutation Examples
• Extra parts:
 Mutation Examples
• Extra parts:

Polydactyl
 Mutation Examples
• Extra parts:
 Mutation Examples
Joined Parts:
• An example of webbed toes sometimes seen in Andersen's Syndrome, caused by a gene
mutation.
 Hensel Twins
Abigail and Brittany
 Mutation Examples
• Just plain odd:

pig dog
 Mutation Trickery
 Looks like but isn’t a mutation:
• This is not a gene mutation. This poor turtle spent a great
deal of its life wrapped up in a milk ring or some other,
probably plastic, man made piece of trash.
 Mutation Trickery or
Genetic Engineering?
Science Ethics: British scientists will be allowed to
• Gene therapy has taken a new turn as
research devastating diseases such as Alzheimer's and
"hybrid" gene "mutations" are
Parkinson's using being
purposefully human-animal
sought out in embryos, after the House
of Commons
sciencerejected
labs acrossathe
ban yesterday.
world.
• Breeding
the
Mutant
Gene
Humans could mutate into their
most basic forms.