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