• 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
3. Chemicals & UV radiation cause mutations
4. Many mutations are repaired by enzymes(DNA polymerase)

Consequence of Mutations
• Most mutations are
• Many are
• Some are
• A few may be

• 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

• Changes in chromosome structure
• Changes in chromosome number
• Relatively small changes in DNA structure
• Occur within ONE particular gene
8

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

• Five types exist:
– Deletion
– Inversion
– Translocation
– Nondisjunction
– Duplication

• Due to breakage
• A piece of a chromosome is lost

• Chromosome segment breaks off
• Segment flips around backwards
• Segment reattaches

• Occurs when a gene sequence is repeated

• Involves two chromosomes that aren’t homologous
• Part of one chromosome is transferred to another chromosomes

• Failure of chromosomes to separate during meiosis
• Causes gamete to have too many or too few chromosomes
• Disorders:
– Down Syndrome – three 21 st chromosomes
– Turner Syndrome – single X chromosome
– Klinefelter’s Syndrome – XXY chromosomes

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
• 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

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
• One base is
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

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 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.

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

• 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

One base is added to the DNA segment
Causes a frameshift Insertion

• 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
.

– 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.

• Original:
– The fat cat ate the wee rat .
• Frame Shift (“a” added):
– The fat c a a 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

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
NormalDNA: TAG TAA AAA CCT CAC mRNA: AUC AUU UUU GGA GUG
Cystic DNA: TAG TAA CCT CAC
FibrosismRNA: 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
• 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

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 research devastating diseases such as Alzheimer's and
Parkinson's using human-animal embryos, after the House science labs across the world.
of Commons rejected a ban yesterday.
• Breeding the
Mutant
Gene

Humans could mutate into their most basic forms.