Gene Mutation. Mutation Mutation: change in DNA sequence Causes of mutation: Spontaneous Due to...
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Transcript of Gene Mutation. Mutation Mutation: change in DNA sequence Causes of mutation: Spontaneous Due to...
Gene Mutation Gene Mutation
MutationMutation
Mutation: change in DNA sequenceMutation: change in DNA sequence
Causes of mutation:Causes of mutation:
SpontaneousSpontaneous Due to naturally-Due to naturally-occurring errors in occurring errors in DNA replicationDNA replication
InducedInduced Due to exposures to Due to exposures to radiation or chemical radiation or chemical mutagensmutagens
Spontaneous MutationSpontaneous Mutation
Spontaneous mutation in gene for a blood clottingSpontaneous mutation in gene for a blood clottingfactor, leading to hemophilia. factor, leading to hemophilia.
Point MutationsPoint Mutations
Point mutation: change in one or a few Point mutation: change in one or a few DNA nucleotidesDNA nucleotides
Substitution Substitution One nucleotide is replaced One nucleotide is replaced by anotherby another
DeletionDeletion One or more nucleotides One or more nucleotides are removedare removed
InsertionInsertion One or more nucleotides One or more nucleotides are addedare added
DuplicationDuplication Nucleotides are repeated Nucleotides are repeated within a genewithin a gene
Substitutions Substitutions
NameName SubstitutionSubstitution ExampleExample
Transition Transition change to same change to same type of basetype of base
PurinePurinepurinepurine
PyrimidinePyrimidinepyrimidinepyrimidine
ATATGCGC
TransversionTransversionchange to different change to different type of basetype of base
PurinePurinepyrimidinepyrimidine
PyrimidinePyrimidinepurinepurine
ATATCGCG
Examples of SubstitutionsExamples of Substitutions
TransitionTransition TransversionTransversion
DNADNATop Top strand is strand is templatetemplate
3’-T-T-C-5’3’-T-T-C-5’5’-A-A-G-3’5’-A-A-G-3’
3’-T-C-C-5’3’-T-C-C-5’5’-A-G-G-3’5’-A-G-G-3’
3’-T-T-C-5’3’-T-T-C-5’5’-A-A-G-3’5’-A-A-G-3’
3’-T-G-C-5’3’-T-G-C-5’5’-A-C-G-3’5’-A-C-G-3’
RNA RNA
codoncodon
5’-A-A-G-3’5’-A-A-G-3’ 5’-A-G-G-3’5’-A-G-G-3’ 5’-A-A-G-3’5’-A-A-G-3’ 5’-A-C-G-3’5’-A-C-G-3’
AminoAmino
AcidAcid
lysinelysine argininearginine lysinelysine threoninethreonine
Effects of Substitutions Effects of Substitutions on the Protein Sequenceon the Protein Sequence
TypeType DefinitionDefinition ExampleExample(codons are shown)(codons are shown)
SilentSilent Change to a different codon Change to a different codon for the SAME AMINO ACIDfor the SAME AMINO ACID
AGGAGG CGG CGG
Arg ArgArg Arg
SynonymousSynonymous Change to a chemically-Change to a chemically-SIMILAR AMINO ACIDSIMILAR AMINO ACID
AAAAAA AGA AGA
Lys ArgLys Arg
MissenseMissense Change to a chemically-Change to a chemically-DIFFERENT AMINO ACIDDIFFERENT AMINO ACID
AAAAAA GAA GAA
Lys GluLys Glu
NonsenseNonsense Change to a stop codon, Change to a stop codon, SHORTENS THE PROTEINSHORTENS THE PROTEIN
CAGCAG UAG UAG
Gln StopGln Stop
Applying Your KnowledgeApplying Your Knowledge
The mutation that leads The mutation that leads to Sickle-cell Disease to Sickle-cell Disease (Hb(HbSS) is a) is a
1.1. Silent MutationSilent Mutation
2.2. Synonymous mutationSynonymous mutation
3.3. Missense MutationMissense Mutation
4.4. Nonsense MutationNonsense Mutation
5.5. None of these None of these
HbS
HbA
Applying Your KnowledgeApplying Your Knowledge
The mutation that leads The mutation that leads to the insertion of valine to the insertion of valine into Hbinto HbSS is due to a is due to a
1.1. TransitionTransition
2.2. TransversionTransversion
3.3. Both a transition and a Both a transition and a transversiontransversion
4.4. Neither a transition nor a Neither a transition nor a transversiontransversion
HbS
Frameshift Mutations Frameshift Mutations
Frameshift mutation: deletion or insertion of nucleotide bases, Frameshift mutation: deletion or insertion of nucleotide bases, not in multiples of threenot in multiples of three
Causes a change in the “reading frame” of codons for the Causes a change in the “reading frame” of codons for the protein sequenceprotein sequence
Original Codon Sequence Original Codon Sequence
Amino acid sequenceAmino acid sequence
AAG-ACU-UAC-CAAAAG-ACU-UAC-CAA
Lys---thr---tyr---glnLys---thr---tyr---gln
Frameshift due to insertionFrameshift due to insertion
Amino acid sequenceAmino acid sequence
AA(A)-GAC-UUA-CCA-AAA(A)-GAC-UUA-CCA-A
Lys----asp---leu---proLys----asp---leu---pro
Insertions in multiplesInsertions in multiplesof three nucleotides of three nucleotides restore the reading restore the reading frame.frame.
Tandem Duplications Tandem Duplications
Tandem duplications: adjacent or nearby Tandem duplications: adjacent or nearby repeat of part of a gene’s sequence repeat of part of a gene’s sequence
Charcot-Marie-Charcot-Marie-Tooth DiseaseTooth Disease
Repeat of Repeat of 1.5 million 1.5 million base pairs base pairs within genewithin gene
Disorder of nervous Disorder of nervous system that affects system that affects nerves directed to nerves directed to muscles in hands and muscles in hands and feet.feet.
Causes a numbing of Causes a numbing of hands and feet, difficulty hands and feet, difficulty walkingwalking
Expanding Triplet Repeats Expanding Triplet Repeats
Expanding Triplet Repeats: increase in number of Expanding Triplet Repeats: increase in number of a specific trinucleotide within a gene from a specific trinucleotide within a gene from generation to generationgeneration to generation
Huntington DiseaseHuntington Disease Repeat of CAG triplet leads to Repeat of CAG triplet leads to repeat of glutamine in the protein repeat of glutamine in the protein Huntingtin.Huntingtin.
Neurodegenerative disorder Neurodegenerative disorder leading to personality changes leading to personality changes and uncontrollable movements. and uncontrollable movements.
Allen(46,13)age 50
Linda(6,22)
Kristen(64,22)age 40
Ann(64,22)age 39
Andrew(69,6)age 37
Debbie(13,6)
Greg(11,19)
Nathaniel(72,19) age 35
Bill(8,12)
Paula(13,12)
Evan(not tested)
Christina(93,7)age 26
Joseph(7,6)
Jama(7,18)
Expansion of the Trinucleotide Repeat for Huntington’s Disease
Applying Your KnowledgeApplying Your Knowledge
A.A. An insertion of one or two nucleotide bases causes An insertion of one or two nucleotide bases causes a _____ .a _____ .
B.B. Replacing one nucleotide with another causes a Replacing one nucleotide with another causes a ____. ____.
C.C. A repeat of part of a gene’s sequence in a nearby A repeat of part of a gene’s sequence in a nearby region is a ______. region is a ______.
1.1. SubstitutionSubstitution2.2. Frameshift MutationFrameshift Mutation3.3. Tandem DuplicationTandem Duplication4.4. Expanding Triplet RepeatExpanding Triplet Repeat
Repair of Repair of DNADNA
Type of DamageType of Damage Repair MechanismRepair Mechanism
Ultraviolet Light Causing Ultraviolet Light Causing Thymine-Thymine DimersThymine-Thymine Dimers
PhotoreactivationPhotoreactivation
Damage caused by Damage caused by chemicals or ultraviolet lightchemicals or ultraviolet light
Excision RepairExcision Repair
Incorrect base inserted in Incorrect base inserted in new strand during replicationnew strand during replication
Mismatch RepairMismatch Repair
Repairing UV-Damaged DNAUse of enzymes to remove and replace region with thymine-thymine dimer
Use of light and enzymes to
reverse thymine-thymine dimers
PhotoreactivationPhotoreactivation
Mismatch Repair: Correcting Errors Mismatch Repair: Correcting Errors
in DNA Replicationin DNA Replication
Xeroderma Pigmentosum: Accumulation Xeroderma Pigmentosum: Accumulation of DNA Damage Leads to Skin Cancerof DNA Damage Leads to Skin Cancer
Applying Your KnowledgeApplying Your Knowledge
A.A. Method of replacing a DNA region that was Method of replacing a DNA region that was damaged by radiation or chemicals damaged by radiation or chemicals
B.B. Method that uses white light to repair thymine-Method that uses white light to repair thymine-thymine dimers produced by ultraviolet radiationthymine dimers produced by ultraviolet radiation
C.C. Method of replacing DNA region where a nucleotide Method of replacing DNA region where a nucleotide was incorrectly placed during replicationwas incorrectly placed during replication
1.1. Mismatch RepairMismatch Repair
2.2. Excision RepairExcision Repair
3.3. PhotoreactivationPhotoreactivation