Download Mutations - Warren County Schools

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
8
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:
mRNA:
amino acid:
TGA TCT ACT
ACU AGA UGA
(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
– NormalDNA: TAG CTT ATT
mRNA: AUC GAA UAA
– Sickle CellDNA: 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
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
The Cause of Cystic
Fibrosis
CFTR
gene
The most common
allele that causes
cystic fibrosis is
missing 3 DNA bases.
As a result, the amino
acid phenylalanine is
missing from the
CFTR protein.
Normal CFTR is a
chloride ion channel
in cell membranes.
Abnormal CFTR
cannot be
transported to the
cell membrane.
The cells in the
person’s airways are
unable to transport
chloride ions. As a
result, the airways
become clogged with a
thick mucus.
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
Causes a
frameshift
Insertion
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-Nacetylhexosaminidase 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 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
codon TAG
omitted.
Normal- one
DNA:
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
allele that causes
cystic fibrosis is
missing 3 DNA bases.
As a result, the amino
acid phenylalanine is
missing from the
CFTR protein.
Normal CFTR is a
chloride ion channel
in cell membranes.
Abnormal CFTR
cannot be
transported to the
cell membrane.
The cells in the
person’s airways are
unable to transport
chloride ions. As a
result, the airways
become clogged with a
thick mucus.
EFFECTS OF MUTATIONS
53
FYI
Normal Male
2n = 46 55
Normal Female
2n = 46 56
Male, Trisomy 21 (Down’s)
2n = 47 57
Female Down’s Syndrome
2n = 47 58
Klinefelter’s Syndrome
2n = 47 59
Turner’s Syndrome
2n = 45
60
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
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
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
research
devastating diseases such as Alzheimer's and
as "hybrid" gene "mutations" are
Parkinson's
using human-animal
after the House
purposefully
being sought out embryos,
in
science
labs across
the world.
of Commons
rejected
a ban
yesterday.
• Breeding
the
Mutant
Gene
Humans could mutate into their
most basic forms.