Mutation – any change in DNA
Mutations
• Mutations are defined as “a sudden genetic
change in the DNA sequence that affects
genetic information”.
• They can occur at the molecular level (genes)
and change a single gene, or at the
chromosome level and affect many genes.
• Things that can cause mutations are called
“mutagens”.
• Known mutagens are ultraviolet light,
cigarette smoking, certain chemicals like
PCB’s.
Effects of Mutations
• Silent mutations - have no effect on the
expression of the gene.
– Causes for this type of mutation:
–It is in a non-coding region (intron)
–It does not change the amino acid sequence
–The change does not affect the folding of the
protein
Heritability of Mutations
It depends on where it occurs
i. Germ line mutations – occur in gametes.
Inheritable (colorblindness, hemophilia)
ii. Somatic mutations – affect body cell, not
inheritable (cancer)
Types of Mutations – mistakes
a) Point Mutations – effects a single gene
i. Substitution
-Missense
-Nonsense
ii. Frameshift
-Insertion
-Deletion
a) Chromosomal mutations – most drastic,
change in structure or # of chromosomes
(affects many genes)
III. Point Mutations
a) Substitution – one base exchanges for
another, affects 1 amino acid
(Ex. GCA-TCA  GCT-TCA
Gene Mutations
The Effects of Point Mutations
► A point mutation is a change in a single base pair in DNA.
– A change in a single nitrogenous base can change the entire structure of a
protein because a change in a single amino acid can affect the shape of the
protein. (SUBSTITUTION)
mRNA
Normal
Protein
Stop
Replace G with A
Point
mutation
mRNA
Protein
Stop
Effects of substitution mutations
• Missense mutations – causes a change in the
amino acid coded for
• Nonsense mutations – causes a stop codon to
occur prematurely
a) Frameshift – affects several amino acids
-Insertion – 1 base is inserted,
affects several amino acids
Ex. (GCA-TCA  GCA-GTC-A
-Deletion – base is removed, affects
several amino acids
Ex. (GCA-TCA  GCT-CA
Gene Mutations
Frameshift Mutations
► What would happen if a single base were lost from a DNA strand?
► A mutation in which a single base is added or deleted from DNA is
called a frameshift mutation because it shifts the reading of
codons by one base.
– As a result, every codon after the deleted base would be different.
Deletion of U
mRNA
Protein
Chromosome mutations
Nondisjunction – incomplete
chromosome division during
meiosis; results in gametes with too
many or too few chromosomes.
Ex: Down syndrome is caused by an
extra #21 chromosome
Polyploidy
Aneuploidy
Down’s Syndrome
•Trisomy 21
•1 in 700 births
•Mental
retardation
•Males are sterile
but females are
not
Likelihood of chromosomal
mutations
1 in 1700 for mothers < 20.
1 in 1400 for mothers >20<30.
1 in 750 for mothers >30<35.
1 in 16 for mothers >45.
WHY a positive correlation between risk of chromosomal mutation and maternal
age?
• Sex chromosome disorders – occurs as a
result of nondisjunction of the sex
chromosomes
• Ex: Turner’s syndrome – X-; Klinefelter’s
syndrome – XXY.
Klinefelter’s Syndrome
•XXY
•1 in 1,000
•Usually sterile because of
low sperm count
•Tall, sparse body hair
•Suffer from gynecomastiamale breast tissue
•Testosterone treatments
Turner’s Syndrome
•XO genotype—Monosomy X
•1 in 2,500 births
•Short, sterile
•75% result in non-disjunction
from the father
Other Chromosomal Mutations
• Affect many different genes
• Caused by errors in meiosis or environmental
disturbances
–Translocation – occurs when a
piece of one chromosome breaks
off and attaches to a
nonhomologous chromosome
–Inversion – occurs when a piece of
one chromosome breaks off, flips,
and reattaches to the same
chromosome
–Deletion – occurs when a piece
of a chromosome breaks off
and is lost
–Duplication – occurs when a
segment of a chromosome is
repeated