Download Mutations

Mutations
Sickle Cell Anemia
Mutations


Can be a change in
the DNA base
sequence or a
change in a
chromosome
Mutant- someone
who has a mutation
Consequences of
Mutations

Mutations can be
– Helpful
Ex: Give immunity to HIV
 Ex: Give immunity to infectious diseases

– Harmless
– Harmful

Ex: Disease causing mutations (some have to
be in homozygous form)
What do Mutations do?

Can stop or slow the production of a
protein
– Ex:

Cause a protein to overproduce
– Ex:

Impair a protein’s function
– Ex:
When can Mutations
happen?


Germline mutation- happens before meiosis;
affects all cells in the new organism
Somatic mutation- happens before mitosis;
after only immediate daughter cells and
their descendents
– More severe the earlier it occurs
– Creates a mosaic
– Can lead to some forms of cancer
Spontaneous Mutations

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Change occurs with no outside
influence
Often occurs because of a mismatch in
base pairs during replication
Results in de novo mutations
Mutation Rates


Different in different genes
Depends on
– Gene size
– Gene location
– Gene sequence
Mutation Hot Spots

Sequence Regions
– That are repetitive
– Symmetrical or
repeated sequences
on the same strand
– Palindromessequence that reads
the same forward
and backward
Sections confuse
replication enzymes
Mutagen

Substance causing
a mutation
– Chemicals
– Radiation


Exposure can be
accidental or
purposeful
It can also come
from the natural
environment
Huntington’s Disease
Types of Mutations

Point mutations- change of a single base
– Transition- exchange of one pyrimidine for
another or one purine for another
– Transversion- exhange of a pyrimidine for a
purine or vice versa
– Missense mutation- changes one amino acid in
polypeptide chain
– Nonsense mutation- creates a stop codon in the
middle of the polypeptide chain
– Splice site mutations- alters the splicing of the
pre-mRNA
Types of Mutation (cont)

Frameshift mutations- move the
reading frame; can be point
mutations; all amino acids after
mutation can be affected
– Insertion- addition of bases

Tandem duplication- repetition of a sequence
placed very close to the original
– Deletion- removal of bases
Expanding Repeats



Repeated section of
DNA is replicated
incorrectly causing
extra repeats
Repeats are added to
during every
generation (higher
severity; earlier onset)
Repeats often create
symptoms when they
reach higher than 40
Wild type
"Normal Gene"
THE ONE BIG FLY HAD ONE RED EYE
Missense
THQ ONE BIG FLY HAD ONE RED EYE
Nonsense
THE ONE BIG
Frameshift
THE ONE QBI GFL YHA DON ERE DEY
Deletion
THE ONE BIG HAD ONE RED EYE
Duplication
THE ONE BIG FLY FLY HAD ONE RED EYE
Insertion
THE ONE BIG WET FLY HAD ONE RED EYE
Expanding
(P) THE ONE BIG FLY HAD ONE RED EYE
Expanding
(F1) THE ONE BIG FLY FLY FLY HAD ONE RED
EYE
Expanding
(F2) THE ONE BIG FLY FLY FLY FLY FLY FLY HAD
ONE RED EYE
Other Causes of
Mutations

Pseudogenes
– Replicate of gene made at earlier time
– Currently not used (collected enough
mutations)
– May still be close enough to cross over
with real gene causing mutations in real
gene

Transposons (jumping genes)
– Jump into working gene causing mutation
Xeroderma Pigmentosum
Minimizing the Effects of
Mutation

Position
– Change in third position often does nothing
– Change in second position often either does nothing
or changes one amino acid for a similar one

Conditional mutation
– Mutation only affects the
phenotype under certain
conditions

Stem cell DNA
– Stem cell may retain old template DNA strands and
send new strands into progenitor cell
DNA Repair:
Photoreactivation


DNA is damaged by UVB
wavelengths
Forms thymine dimers
– extra covalent bond between thymines
next to each other on the same strand
– forms kinks in DNA; disrupts replication
and transcription


Enzymes called photolyases absorb
energy from light and break these
bonds
Humans do not use this
DNA Repair: Excision
Repair



Enzymes snip out section with pyrimidine
dimers
DNAP fills in gap with correct nucleotides
Humans have two types
– Nucleotide excision repair
Used for many types of damage
 Repairosome- group of enzymes that cut out and
replace up to 30 nucleotides

– Base excision repair
Used for oxidative damage
 Replaces up to 5 nucleotides at a time

Nucleotide Excision Repair
Base Excision Repair
DNA Repair: Mismatch
Repair


Repairs errors that
occur because of
replication
Enzymes look for
loops in DNA (sign
of mismatching)
and cut out and
repair bases