4 ways to classify mutations
- whether they’re heritable
- how they arise
- effects on gene function
- the type of mutation
Mutations are an important source of…
genetic diversity
Wildtype alleles
more abundant allele
Mutant alleles
more rare allele
Spontaneous mutation
occur randomly with no known cause
- arise in spontaneous manner (replication error/transposons)
- occur infrequently compared to induced mutations
Induced mutation
arise due to exposure to physical & chemical mutagenic agents, radiation
- increase freq of mutation rates several fold compared to spontaneous mutations
Loss of function mutation
Reduces or destroys protein function
- can be dominent (hapo-insufficient)
- can be recessive (hapo-sufficient)
2 types of LOF mutations
- null (amorphic): complete loss of protein function
- hypomorphic: incomplete; reduced activity
Gain of function mutation
Increased activity or new function; wrong place wrong time
- almost always dominant
3 types of GOF mutations
- hypermorphic: more activity/more efficient protein
- neomorphic: generates a new function
- antimorphic: prevents normal protein from performing normal homeostatic function
Tp53
- tumour protein 53 (important tumour suppressor)
- a transcription factor that functions as the gatekeeper of cell cycle progression
- p53 arrests cell cycle if there’s DNA damage
p53 in normal homeostasis
- allow cells to repair damage
turn on - apoptosis genes
- DNA repair genes
turn off - cell cycle genes
DECREASED proliferation
p53 LOF (null)
- INCREASED proliferation
- in cancer, most p53 LOF mutation occur in DBD
(dna binding domain)
p53 GOF
- anti-morphic
- surpasses the function of WT p53
- exhibit same phenotypes as p53 null cells
- reduced expression apoptosis/repair
- up-regulation of cell cycle genes
Types of mutations
- single nucleotide (point mutation)/ few bp
- chromosomal rearrangements
- changes in chromosome number (aneuploidy)
Point mutations
- change in DNA seq without changing the open reading frame
- single base pair substitutions
3 types of point mutations
- nonsense: code for a STOP codon (truncate protein)
- missense: code for a different amino acid resulting in non func protein/protein w different func
- silent: code for the same or different amino acid but there’s no func change in protein
central dogma
- specified by the genetic code
- genetic code: set of nucleotide triplicate that code for aa or translate stop signal
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Module 413
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Module 5 - Part 112
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Module 5 - Part 219
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Module 6 - Part 17
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Module 6 - Part 214
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Module 1 - Part 118
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Module 1 - Part 211
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Module 2 - Part 113
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Module 2 - Part 210
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Module 3 - Part 16
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Module 3 - Part 215
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Module 7 - Part 118
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Module 7 - Part 26
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Module 8 - Part 112
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Module 8 - Part 219
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Module 9 - Part 117
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Module 9 - Part 244
