CS262 Discussion Section 4

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CS262 Discussion Section 4
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Agenda for today

• Brief coverage of mutations.
• Discussion of material related to HMMs (on the
  blackboard)

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Mutation

• A mutation is a permanent change in the DNA
  sequence.
• It can have profound consequences
• It can severely compromise an organisms fitness
  if the change occurs in a vital position in the
  DNA sequence.
• A single nucleotide change causes the disease
  sickle-cell 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

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Somatic vs Germ line cell lineages
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Somatic vs Germ line mutations

• 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 organisms offspring.
• 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.

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Classification of mutations according to the
length of the DNA sequence affected

• Point mutation
• A single nucleotide is affected

• Segmental mutation
• Several adjacent nucleotides are affected.

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Classification of mutations according to the
effect on the DNA molecule

• 1. Substitution The replacement of one
  nucleotide by another

TCTCGCATGGTAGGT
5-
-3
AGAGCGTACCATCCA
-5
3-
TCTCGCATGGTAGAT
5-
-3
-5
3-
AGAGCGTACCATCTA
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Classification of mutations according to the
effect on the DNA molecule

• Substitution mutations in protein-coding regions
  are classified according to their effect on the
  protein synthesized.
• Synonymous No change in the amino-acid
  specified.
• 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
• 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.

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Classification of mutations according to the
effect on the DNA molecule

• 2. Deletion A block of one or more nucleotide
  pairs is lost from a DNA molecule.

TCTCGCATGGTAGGT
5-
-3
AGAGCGTACCATCCA
-5
3-
TCTCTGGTAGGT
5-
-3
-5
3-
AGAGACCATCCA
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Classification of mutations according to the
effect on the DNA molecule

• 3. Insertion The addition of one or more
  nucleotide pairs.

TCTCGCATGGTAGGT
5-
-3
AGAGCGTACCATCCA
-5
3-
TCTCAAGCATGGTAGGT
5-
-3
-5
3-
AGAGTTGCAACCATCCA
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Indels

• 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.

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Frameshift mutation

• Shift in the reading frame The coding sequence
  downstream of the gap will be read in the wrong
  phase.
• 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.

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Classification of mutations according to the
effect on the DNA molecule

• Inversion 180 degree rotation of a segment of
  the DNA molecule.

Site of inversion
TCTCGCATGGTAGGT
5-
-3
AGAGCGTACCATCCA
-5
3-
TCTTACCATGCGGGT
5-
-3
-5
3-
AGAATGGTACGCCCA
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Classification of mutations according to the
effect on the DNA molecule

• 5. Recombination The exchange of a sequence with
  another.

5-AACT-3
5-AACG-3
3-TTGC-5
3-TTGA-5
5-CACG-3
5-CACT-3
3-GTGA-5
3-GTGC-5
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Spatial distribution of mutations

• 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

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