LESSON 3: MUTATIONS Flashcards
Individuals showing phenotypic
differences in one or more particular characters
Genetic Variants
Change in the DNA sequence of a gene
Mutation
Grouping into new combinations
Recombination
WOBBLE HYPOTHESIS - who and when?
Francis Crick, 1996
We only have ___ tRNA
20
Also called silent mutations
SYNONYMOUS MUTATIONS
Also called nonsynonymous mutations
MISSENSE MUTATIONS
The codon for one amino acid is changed into a
translation-termination codon (stop codon)
NONSENSE MUTATIONS
● There is an introduction or taking out of a new base
in a sequence
● Affects all codons downstream of the mutation,
resulting in a frameshift
INDEL MUTATIONS
● Functional consequences in this region depend on
whether it disrupts or creates a binding site
● Many elicit little to no phenotypic change
NONCODING REGION MUTATIONS
SPONTANEOUS MUTATIONS
SPOTANEOUS: ERRORS IN DNA REPLICATION
SPONTANEOUS LESIONS
INDUCED MUTATIONS
INDUCED: BASE ANALOG INCORPORATION
INDUCED: SPECIFIC MISPAIRING
INDUCED: INTERCALATING AGENTS
INDUCED: BASE DAMAGE
● ____ → Takes something that looks
like a base
● ____ → changes the base → not
functional
● ____ → destroy the base
Base replacement
Base alteration
Base damage
● Base replacement
● Some chemical compounds are sufficiently similar
to the normal bases of DNA and are called base
analogs
INDUCED: BASE ANALOG INCORPORATION
● Base alteration
● Alteration of a base such that it will form a specific
mispair
INDUCED: SPECIFIC MISPAIRING
● Planar molecules that mimic base pairs
● Can slip in between stacked nitrogen bases
INDUCED: INTERCALATING AGENTS
● Damage to one or more bases
● No specific base pairing is possible, resulting in a
replication block
INDUCED: BASE DAMAGE
genetic variants controlling the same trait
Allele
multiples of the basic chromosome set
Euploid
one or more chromosomes missing or
in surplus
Aneuploid
Extra set/s of chromosomes
Polyploid
CHANGE IN CHROMOSOME NUMBER
● Changes in whole sets of chromosomes
● Having more or less than normal number of sets
● Monoploid and Polyploids
ABERRANT EUPLOIDY
CHANGE IN CHROMOSOME NUMBER
● Chromosome number differs from the wild type by a
part of the chromosome set
● Can have a number greater or smaller than the
wildtype
ANEUPLOIDY
Cause of most aneuploidy in the course of meiosis
or mitosis
NONDISJUNCTION
● Missing one copy of a chromosome
● Monosomic autosomes = die in utero
MONOSOMY (2n-1)
● Has one extra copy of a chromosome
Abnormality/death
TRISOMY (2n+1)
Why are aneuploids so much more abnormal than polyploids?
Due to gene balance → the body is
dependent on ratios (how much it
makes/breaks down)
■ The problem with the ratio → you
would get sick
INVERSIONS
● ______: does not involve centromeres, the
change is away from it
● ______: Affects the centromere
Paracentric
Pericentric
trading of acentric fragments of two nonhomologous chromosomes
RECIPROCAL TRANSLATION
CANCER MUTATIONS
_______ when they have a
gain-of-function mutation, become oncogenes
Proto-oncogenes
CANCER MUTATIONS
____ become cancerous
when they have loss-of-function mutations
Tumor-suppressor genes
Tumor-suppressor gene
“Guardian of the Genome”
50% of human tumors lack a functional ____ gene
p53
Naturally occurring mutations that
arise in all cells
SPONTANEOUS
Arise through the action of
mutagens that increase the rate of
mutations
INDUCED
TRANSITIONS
● Purine→ ___
● Pyrimidine → ___
- Purine
- pyrimidine
TRANSVERSIONS
Purine → ___(vice versa)
pyrimidine
Functional Consequences
● The genetic code is degenerate (___)
Wobble hypothesis
Functional Consequences
There exists stop codons (___)
Translation termination
Two types:
○ conservative
■ Changes into the amino acid of the same type
● ___→ ___ (both are basic amino acids)
Lysine → histidine
Two types:
○ conservative
■ Changes into the amino acid of the same type
● ___→ ___(both are non-polar)
○ nonconservative
Proline → Valine
Two types:
○ nonconservative
■ From one amino acid into an amino acid of the different type
● ___→ ___ (acidic base to a non-polar)
Glutamate → Valine
Results in ________ → shorter protein product
○ Protein will be not functional
premature chain termination
Single base pair changes that INACTIVATE proteins are often due to _____
splice site mutations
SPOTANEOUS: ERRORS IN DNA REPLICATION
Structual isomers of the bases and can co-exist in a solution, and would just interchange with one
another at any point
TAUTOMERS
SPONTANEOUS LESIONS
● Loss of a purine base
● Interruption of the N-glycosidic bond by hydrolysis
DEPURINATION
SPONTANEOUS LESIONS
● Loss of an amino group (NH2) from cytosine
DEAMINATION
SPONTANEOUS LESIONS
● Reactive oxygen species are produced by normal aerobic metabolism
OXIDATIVE DAMAGE
Some chemical compounds are sufficiently similar
to the normal bases of DNA and are called ___
base analogs
Smallest type of mutations one can have but
equally have big effects
POINT MUTATIONS
