MutationsMutations

Sickle Cell Anemia

MutationsMutations

Can be a change Can be a change in the DNA base in the DNA base sequence or a sequence or a change in a change in a chromosomechromosome

Mutant- someone Mutant- someone who has a who has a mutationmutation

Consequences of Consequences of MutationsMutations Mutations can beMutations can be

– HelpfulHelpful Ex: Give immunity to HIVEx: Give immunity to HIV Ex: Give immunity to infectious diseasesEx: Give immunity to infectious diseases

– HarmlessHarmless– Harmful Harmful

Ex: Disease causing mutations (some Ex: Disease causing mutations (some have to be in homozygous form)have to be in homozygous form)

What do Mutations do?What do Mutations do?

Can stop or slow the production Can stop or slow the production of a proteinof a protein– Ex: Ex:

Cause a protein to overproduceCause a protein to overproduce– Ex:Ex:

Impair a protein’s functionImpair a protein’s function– Ex:Ex:

When can Mutations When can Mutations happen?happen? Germline mutation- happens before Germline mutation- happens before

meiosis; affects all cells in the new meiosis; affects all cells in the new organismorganism

Somatic mutation- happens before Somatic mutation- happens before mitosis; after only immediate daughter mitosis; after only immediate daughter cells and their descendents cells and their descendents – More severe the earlier it occursMore severe the earlier it occurs– Creates a mosaicCreates a mosaic– Can lead to some forms of cancerCan lead to some forms of cancer

Spontaneous Mutations Change occurs with no outside Change occurs with no outside

influenceinfluence

Often occurs because of a Often occurs because of a mismatch in base pairs during mismatch in base pairs during replicationreplication

Results in de novo mutationsResults in de novo mutations

Mutation RatesMutation Rates

Different in different genesDifferent in different genes Depends onDepends on

– Gene sizeGene size– Gene location Gene location – Gene sequenceGene sequence

Mutation Hot SpotsMutation Hot Spots

Sequence Regions Sequence Regions – That are repetitiveThat are repetitive– Symmetrical or Symmetrical or

repeated sequences repeated sequences on the same strandon the same strand

– Palindromes- Palindromes- sequence that reads sequence that reads the same forward the same forward and backwardand backward

Sections confuse Sections confuse replication enzymesreplication enzymes

Mutagen Mutagen

Substance causing Substance causing a mutationa mutation– ChemicalsChemicals– Radiation Radiation

Exposure can be Exposure can be accidental or accidental or purposeful purposeful

It can also come It can also come from the natural from the natural environmentenvironment

Huntington’s Disease

Types of MutationsTypes of Mutations

Point mutations- change of a single Point mutations- change of a single basebase– Transition- exchange of one pyrimidine for Transition- exchange of one pyrimidine for

another or one purine for anotheranother or one purine for another– Transversion- exhange of a pyrimidine for Transversion- exhange of a pyrimidine for

a purine or vice versaa purine or vice versa– Missense mutation- changes one amino Missense mutation- changes one amino

acid in polypeptide chainacid in polypeptide chain– Nonsense mutation- creates a stop codon Nonsense mutation- creates a stop codon

in the middle of the polypeptide chainin the middle of the polypeptide chain– Splice site mutations- alters the splicing of Splice site mutations- alters the splicing of

the pre-mRNAthe pre-mRNA

Types of Mutation Types of Mutation (cont)(cont) Frameshift mutations- move the Frameshift mutations- move the

reading frame; can be point reading frame; can be point mutations; all amino acids after mutations; all amino acids after mutation can be affectedmutation can be affected– Insertion- addition of basesInsertion- addition of bases

Tandem duplication- repetition of a Tandem duplication- repetition of a sequence placed very close to the sequence placed very close to the originaloriginal

– Deletion- removal of basesDeletion- removal of bases

Expanding RepeatsExpanding Repeats

Repeated section of Repeated section of DNA is replicated DNA is replicated incorrectly causing incorrectly causing extra repeatsextra repeats

Repeats are added to Repeats are added to during every during every generation (higher generation (higher severity; earlier onset)severity; earlier onset)

Repeats often create Repeats often create symptoms when they symptoms when they reach higher than 40reach higher than 40

Wild type"Normal Gene"

THE ONE BIG FLY HAD ONE RED EYE

Missense THQ ONE BIG FLY HAD ONE RED EYE

Nonsense THE ONE BIG

Frameshift THE ONE QBI GFL YHA DON ERE DEY

Deletion THE ONE BIG HAD ONE RED EYE

Duplication THE ONE BIG FLY FLY HAD ONE RED EYE

Insertion THE ONE BIG WET FLY HAD ONE RED EYE

Expanding (P) THE ONE BIG FLY HAD ONE RED EYE

Expanding(F1) THE ONE BIG FLY FLY FLY HAD ONE

RED EYE

Expanding(F2) THE ONE BIG FLY FLY FLY FLY FLY FLY

HAD ONE RED EYE

Other Causes of Other Causes of MutationsMutations PseudogenesPseudogenes

– Replicate of gene made at earlier timeReplicate of gene made at earlier time– Currently not used (collected enough Currently not used (collected enough

mutations)mutations)– May still be close enough to cross over May still be close enough to cross over

with real gene causing mutations in real with real gene causing mutations in real genegene

Transposons (jumping genes)Transposons (jumping genes)– Jump into working gene causing mutationJump into working gene causing mutation

Xeroderma Pigmentosum

Minimizing the Effects Minimizing the Effects of Mutationof Mutation

PositionPosition– Change in third position often does nothingChange in third position often does nothing– Change in second position often either does nothing Change in second position often either does nothing

or changes one amino acid for a similar oneor changes one amino acid for a similar one Conditional mutationConditional mutation

– Mutation only affects the Mutation only affects the

phenotype under certain phenotype under certain

conditionsconditions Stem cell DNAStem cell DNA

– Stem cell may retain old template DNA strands and Stem cell may retain old template DNA strands and send new strands into progenitor cellsend new strands into progenitor cell

DNA Repair: DNA Repair: PhotoreactivationPhotoreactivation

DNA is damaged by UVB DNA is damaged by UVB wavelengthswavelengths

Forms thymine dimersForms thymine dimers– extra covalent bond between thymines extra covalent bond between thymines

next to each other on the same strandnext to each other on the same strand– forms kinks in DNA; disrupts replication forms kinks in DNA; disrupts replication

and transcriptionand transcription Enzymes called photolyases absorb Enzymes called photolyases absorb

energy from light and break these energy from light and break these bondsbonds

Humans do not use thisHumans do not use this

DNA Repair: Excision DNA Repair: Excision RepairRepair Enzymes snip out section with pyrimidine Enzymes snip out section with pyrimidine

dimersdimers DNAP fills in gap with correct nucleotidesDNAP fills in gap with correct nucleotides Humans have two typesHumans have two types

– Nucleotide excision repairNucleotide excision repair Used for many types of damageUsed for many types of damage Repairosome- group of enzymes that cut out and Repairosome- group of enzymes that cut out and

replace up to 30 nucleotidesreplace up to 30 nucleotides

– Base excision repairBase excision repair Used for oxidative damageUsed for oxidative damage Replaces up to 5 nucleotides at a timeReplaces up to 5 nucleotides at a time

Nucleotide Excision Nucleotide Excision RepairRepair

Base Excision Repair Base Excision Repair

DNA Repair: Mismatch DNA Repair: Mismatch RepairRepair

Repairs errors Repairs errors that occur that occur because of because of replicationreplication

Enzymes look for Enzymes look for loops in DNA (sign loops in DNA (sign of mismatching) of mismatching) and cut out and and cut out and repair basesrepair bases