Transcript CS262 Discussion Section 4

CS262 Discussion
Section 4
Agenda for today
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Brief coverage of mutations.
Discussion of material related to HMMs (on
the blackboard)
Mutation
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A mutation is a permanent change in the DNA
sequence.
It can have profound consequences
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It can severely compromise an organism’s fitness
if the change occurs in a vital position in the DNA
sequence.
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A single nucleotide change causes the disease sicklecell anemia.
Note: We will not discuss the molecular
mechanisms responsible for the creation of
mutations.
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http://www.defiers.com/sc.jpg
Somatic vs Germ line cell
lineages
Somatic vs Germ line
mutations
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A mutation that occurs in the germ line, is
passed on to the next generation.
A mutation in a somatic cell is not transmitted
to the organism’s offspring.
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But it may have unfortunate consequences for the
individual in whom it occurs (such as cancer)
In tracking the genetic changes that
accumulate during evolution, we concentrate
on events that occur in the germ line.
Classification of mutations
according to the length of the
DNA sequence affected
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Point mutation
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A single nucleotide is
affected
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Segmental
mutation
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Several adjacent
nucleotides are
affected.
Classification of mutations
according to the effect on the
DNA molecule
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1. Substitution: The replacement of one
nucleotide by another
5’- TCTCGCATGGTAGGT -3’
3’- AGAGCGTACCATCCA -5’
5’- TCTCGCATGGTAGAT
3’- AGAGCGTACCATCTA
-3’
-5’
Classification of mutations
according to the effect on the
DNA molecule
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Substitution mutations in protein-coding
regions are classified according to their effect
on the protein synthesized.
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Synonymous: No change in the amino-acid
specified.
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Most of them are silent. (no changes detected at the
amino acid level)
A synonymous mutation may not always be silent.
Non-synonymous: Change in the amino-acid.
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Non-synonymous (amino-acid altering)
mutations could be either
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Missense mutation: changes the affected codon
into a codon that specifies a different amino acid
from the one previously encoded.
Nonsense mutation: changes a sense codon into
a termination codon, thus prematurely ending the
translation process and ultimately resulting in the
production of a truncated protein.
Classification of mutations
according to the effect on the
DNA molecule
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2. Deletion: A block of one or more nucleotide
pairs is lost from a DNA molecule.
5’- TCTCGCATGGTAGGT -3’
3’- AGAGCGTACCATCCA -5’
5’- TCTCTGGTAGGT -3’
3’- AGAGACCATCCA -5’
Classification of mutations
according to the effect on the
DNA molecule
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3. Insertion: The addition of one or more
nucleotide pairs.
5’- TCTCGCATGGTAGGT -3’
3’- AGAGCGTACCATCCA -5’
5’- TCTCAAGCATGGTAGGT
3’- AGAGTTGCAACCATCCA
-3’
-5’
Indels
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Deletions and insertions are collectively
referred to as indels, because when two
sequences are compared, it is impossible to
tell whether a deletion has occurred in one, or
an insertion has occurred in the other.
In a coding region, an indel that is not a
multiple of 3 nucleotides causes a frameshift
mutation.
Frameshift mutation
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Shift in the reading frame: The coding
sequence downstream of the gap will be read
in the wrong phase.
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Indels may not only introduce numerous amino
acid changes…
… but may also obliterate the termination codon…
…or bring into phase a new stop codon, resulting
in a protein of abnormal length.
Classification of mutations
according to the effect on the
DNA molecule
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Inversion: 180 degree rotation of a segment
of the DNA molecule.
Site of inversion
5’- TCTCGCATGGTAGGT -3’
3’- AGAGCGTACCATCCA -5’
5’- TCTTACCATGCGGGT -3’
3’- AGAATGGTACGCCCA -5’
Classification of mutations
according to the effect on the
DNA molecule
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5. Recombination: The exchange of a
sequence with another.
5’-AACT-3’
3’-TTGA-5’
5’-CACG-3’
3’-GTGC-5’
5’-AACG-3’
3’-TTGC-5’
5’-CACT-3’
3’-GTGA-5’
Spatial distribution of
mutations
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Mutations do not occur randomly throughout
the genome. Some regions are more prone to
mutate than others (hotspots of mutation).
One such hotspot is the dinucleotide 5’-CG-3’
(also called CPG) in which cytosine is
frequently methylated in many animal
genomes, changing it to 5’-TG’-3’