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Chapter 12
Gene Mutation
Effects of Mutations
• Prevents a protein from
forming
Lack of dystrophin causes
muscle cells to weaken.
• Lowers amount of a
protein
Blood clots very slowly
due to too little clotting
factor
Skin blisters form because
A.A substitution prevents
layers of skin to connect
Extra bases in Huntington
gene adds amino acids,
altering function to cause
brain degeneration
• Alters a protein
• Changes the function of
a protein
• Germline Mutation – mutation that affects all
cells because the mutation occurred prior to
meiosis.
• Somatic mutation – change happens prior to
DNA replication of mitotic division.
10.2 Causes of Mutation
• Mutagen – An agent that causes a mutation
Spontaneous Mutation
- Tautomers – Different forms of the same
nitrogen base. (Stable vs. Unstable)
Spontaneous Mutation Rate
• Highest mutation rate
– Neurofibromatosis Type 1 (Large Gene –
Dominant inheritance)
– Mitochondrial Genes
• Lower mutation Rates
– Recessive traits?
– Human genes vs. Bacterial Genes
Mutational Hot Spots
Mutational Hot Spots
• Hot Spots – Areas on a gene that mutate
often.
– Repeat sequences – Replication enzymes might be
“confused”
• Example
– Alkaptonuria
• 35% of the errors occur near CCC repeats
• CCC repeats only account for 9% of the gene
Mutational Hot Spots
• Other stretches of alternating repeats..
– Example ATATATATATATATAT
– Hint: (Think of rho independent transcription.)
• Palindrome Sequences (not be confused with
an inverted repeat!!)
– GAATTC (How is this a Palindrome?)
– CTTAAG
Mutational Hot Spots
• Repeat patterns have
issues with meiosis
– Synapsis issue causes
crossing over problems
causes gametes with
insertion or deletion
issues.
Induced Mutations
• Purpose – We don’t know the function of the
gene until it doesn’t work.
Intentional Use of Mutagens
Alkylating Agents (chemical) – remove a DNA base
and another can be added
Acridines (dye) – base is removed but not replaced
causing a frameshift mutation
Scientist cannot really choose where the mutation
will take place with these processes
Site Directed Mutagenesis
• PCR
– Altered Primer can
target the specific
sequence.
Accidental Mutagens
• Chernobyl
– Soviet Union 1986
– 28 people died due to radiation exposure
– Thyroid Rate in children of Chernobyl has increased tenfold.
• Ionizing Radiation
– Alpha (Least energetic..absorbed by the skin)
• Uranium and Radium
– Beta (Penetrate further than alpha)
• H-3, C-14
– Gamma (Penetrate all the way through the body..most
damaging)
• Plutonium and Cesium…used in weapons & to destroy cancer cells
10.3 Types of Mutations
•
•
•
•
•
•
•
Missense
Nonsense
Frameshift
Deletion
Insertion
Duplication
Expanding Mutations
Psuedogenes: A key to our past…
• http://www.dnatube.com/video/5566/AllAbout-Pseudogenes
Genes can move?!?!
• http://highered.mcgrawhill.com/sites/0072556781/student_view0/ch
apter13/animation_quiz_5.html
• Transposons = “jumping genes”
Expanding Genes
• P generation
(Bad)
F1
(Worse)
F2
(Worst)
Repeating sequences will increase in number
from one generation to another
Allelic Disorders
• Different disease phenotypes caused by
mutations in the same gene.
• NON Example – CFTR ALWAYS CAUSES CYSTIC
FIBROSIS
• EXAMPLE – LAMIN A mutation can cause
progeria, muscular dystrophies, heart disease
Conditional Mutation
• Only has an effect on the phenotype under
certain circumstances.
• G6PD deficiency – Life threatening disease.
• IF YOU EAT FAVA BEANS!