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• Gene Mutation Origins and Repair Processes

GAATTC ? GTATTC A ? a
Skin cancers from Xeroderma pigmentosum, a
recessive hereditary disease caused by a
deficiency in a DNA repair enzyme
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Mutations
Transcription Translation
Gene
DNA
Normal protein gene product
Mutational event
Mutated gene

• Abnormal protein
• gene product
• partially functional
• nonfunctional
• no gene product

• Gene
• nucleotide sequence on a
• chromosome that encodes
• a specific protein

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DNA Mutations An Overview
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Mutations
Heritable changes in base sequences that modify
the information content of DNA
Forward mutation a mutation that changes the
wildtype allele of a gene to a different allele.
The resultant allele can be either dominant or
recessive to the original wildtype
Reverse mutation or reversion a mutation that
causes a mutant allele to revert back to
wildtype.
Remember wild alleles designated with a
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La mayoría de las mutaciones ocurre durante la
replicación del DNA o durante su reparación
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Mistakes during DNA replication can also alter
genetic information
Replication errors are extremely rare, generally
occurring once per 109 base pairs
The rate of replication errors is kept low due to
correction or proofreading activity, which
reduces the error rate to one in 106 bases copied
by DNA polymerase (in vitro)
Both DNA polymerase I and II have
proofreading ability. It is a 3 to 5 nuclease
activity
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Classes of DNA mutations
Substitution base at certain position is
substituted by one of other 3 bases
Transition purine (A/G) for purine or pyrimidine
(C/T) for pyrimidine
Transversion purine (A/G) to pyrimidine (C/T) or
visa versa
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Deletion Mutation block of ONE or
more nucleotide pairs is lost from a DNA molecule
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• Inversion Mutations
• 180 rotation of segment of DNA molecule

• Translocations
• Parts of nonhomologous chromosomes change place

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Overview

• Hereditable change in DNA resulting from change
  in nucleotide sequence
• Mutation changes one allelic form to another and
  is the ultimate source of genetic variation.
• Mutational variation underlies the study of
  genetics.
• Mutations are produced by mutagens or occur
  spontaneously.
• Each base pair has a certain probability of
  undergoing change
• Point mutations include single base-pair
  substitutions, additions or deletions.
• Specialized forms of mutation include expansion
  of trinucleotide repeats and insertion of
  transposable elements.
• Many types of mutation can be repaired.

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Mutation

• Hereditable change in DNA resulting from change
  in nucleotide sequence
• Multiple causes
• DNA replication/repair errors
• Mutagens spontaneous DNA damage
• Insertion of transposons
• Several categories of mutation
• Point mutations
• Swap one base for another insert a base delete
  a base
• Alter the number of copies of a short repeat
• Large insertions into a gene

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Point Mutations

• Single or few base pair changes
• Provide background rate of mutation
• critically important to evolution
• More likely to lead to loss of function than gain
  of function
• Origin of point mutation
• Induced, by geneticist for example
• action of mutagen environmental agent that
  alters nucleotide sequence
• process of inducing mutations by mutagens called
  mutagenesis
• Spontaneous
• arise in absence of known mutagen
• may be caused by errors in DNA replication

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Types of point mutation

• Base substitution
• transition
• A ? G (purine ? purine) (AT ? GC)
• C ? T (pyrimidine ? pyrimidine) (CG ? TA)
• transversion
• purine ? pyrimidine (e.g., A ? C) (AT ? CG)
• Addition or deletion of nucleotide pairs
  (base-pair addition or deletion)
• also called indel mutations

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Molecular Consequences
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Terminación Prematura por mutaciones sin
sentido (non sense)
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Mutaciónes supresoras intragénicas
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Figure 27.27 How an intergenic suppression
mutation can overcome a nonsense mutation.
                                                  
                                               
                                   
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Efecto de mutaciones supresoras intergénicas
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Mutación supresora Ambar
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Mutación supresora Opalo