Transcript Mutations

MUTATIONS
WHAT ARE
MUTATIONS?
• 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
ARE MUTATIONS HELPFUL OR
HARMFUL?
• Mutations happen regularly
• Almost all mutations are
neutral
• Chemicals & UV radiation
cause mutations
• Many mutations are
repaired by enzymes
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)
• Mutagen any thing
• That causes mutations
CAUSES OF MUTATIONS
• Any thing that causes mutations is called
mutagen
• A mutagen that causes mutations resulting in
cancer is carcinogen
• A high frequency UV light contains enough
energy to cause a point mutation. One in
nine canadians will develop cancer at some
point in life.
• X-rays also cause mutaions by breaking the
backbone of DNA
• spontaneous mutations occurring without
chemical
• change or radiation but as a result of errors
made in DNA replication
• Induced mutations may also be caused by
exposure to chemicals. Numerous pesticides
have been linked to deleterious mutations
and have now been banned in Canada and
other parts of the world.
INDUCED MUTATIONS
• Caused by mutagens rather than spontaneous
• Induced mutations may also be caused by exposure to
chemicals. Numerous pesticides have been linked to
deleterious mutations and have now been banned in
Canada and other parts of the world.
• Cystic fibrosis is another example of a genetic disease.
• It is caused by any one of at least 60 different types of
mutations in the CFTR gene. The severity of cystic fibrosis
varies with the location of the mutation. Missense,
splicing, nonsense, and frameshift mutations have been
characterized in the CFTR gene, all causing cystic
fibrosis. The most common mutation is a 3-base-pair
deletion discovered in Toronto at the Hospital for Sick
Children by Dr. Lap-Chee Tsui and his research team.
• Chemicals that resemble DNA can
also cause mutations. This capability
has been taken advantage of in AIDS
therapy.
• Some of the chemicals in AIDS drugs
resemble the nitrogenous bases in
DNA and insert themselves into the
virus’s DNA.When the viral DNA is to
be duplicated, the DNA polymerase
stops because it does not recognize
the substituted chemical as a base.
The progression of the disease is
slowed.
TYPES OF
MUTATIONS
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
• Change in the
nucleotide sequence of
a gene
• May only involve a
single nucleotide
• May be due to copying
errors, chemicals,
viruses, etc.
TYPES OF GENE
MUTATIONS
• Include:
• Point Mutations
• Substitutions
• Insertions
• Deletions
• Frameshift
POINT MUTATION
• Change of a single
nucleotide
• Includes the deletion,
insertion, or
substitution of ONE
nucleotide in a gene
No change
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTTCTCACGCCA
↓
CCAGAAGAGUGCGGU
↓
Pro-Glu-Glu-Cys-Gly
Mutations: Substitutions
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCACCTCACGCCA
↓
CCAGUGGAGUGCGGU
↓
Pro-Arg-Glu-Cys-Gly
Substitutions will only affect a single codon
Their effects may not be serious unless they affect an amino acid that is
essential for the structure and function of the finished protein molecule (e.g.
sickle cell anaemia)
Mutations: Inversion
Inversion mutations, also, only affect a small part of the
gene
Inversion mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
GGTCCTCTCACGCCA
↓
CCAGGAGAGUGCGGU
↓
Pro-Gly-Glu-Cys-Gly
MISSENSE MUTATIONS
• missense mutation a mutation
• that results in the single
substitution
• of one amino acid in the
resulting
• polypeptide
POINT MUTATION
• Sickle Cell
disease is the
result of one
nucleotide
substitution
• Occurs in the
hemoglobin gene
FRAMESHIFT
MUTATION
• Inserting or deleting
one or more nucleotides
• Changes the “reading
frame” like changing a
sentence
• Proteins built
incorrectly
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
GENE MUTATION
ANIMATION
NORMAL MALE
2n = 46
32
NORMAL FEMALE
2n = 46
33
MALE, TRISOMY 21 (DOWN’S)
2n = 47
34
FEMALE DOWN’S SYNDROME
2n = 47
35
KLINEFELTER’S SYNDROME
2n = 47
36
TURNER’S SYNDROME
2n = 45
37