Genetic MutationsAtif Hassan Khirelsied Ph.DFaculty of MedicineInternational University of AfricaInternational University of Africa
MutationsMutationsMutationsMutations• The mutation is defined as a permanentThe mutation is defined as a permanent inheritable change in DNA base sequence.
Types of mutationsTypes of mutations• Chromosomal aberrations • Gene mutations
Chromosomal mutationsChromosomal mutationsChromosomal mutationsChromosomal mutations• Large sections of chromosomes can be altered or shifted leading to changes in thealtered or shifted, leading to changes in the way the genes on them are expressed.
Chromosomal translocationsChromosomal translocationsChromosomal translocationsChromosomal translocations• The interchange of large segments of DNA between two different chromosomes.• This can change expression of genes if a gene is at the translocation break‐point or if it is reattached a new promoter region. p g
Chromosomal inversionsChromosomal inversionsChromosomal inversionsChromosomal inversions• Occur when a region of DNA flips its orientation with respect to the rest of theorientation with respect to the rest of the chromosome. • This can lead to the same problems as• This can lead to the same problems as translocations.
Chromosomal deletionChromosomal deletionChromosomal deletionChromosomal deletion• A large regions of a chromosome may be• A large regions of a chromosome may be deleted, leading to loss of some genes.
Chromosomal nonChromosomal non disjunctiondisjunctionChromosomal nonChromosomal non‐‐disjunctiondisjunctionS ti h l t k f• Sometimes a chromosome can lose track of where it is supposed to go in cell division. • One of the daughter cells will end up with• One of the daughter cells will end up with more or less than its share of DNA.
• When a new cell gets less or more than its share of DNA it will have problems with geneshare of DNA, it will have problems with gene dosage.• Extra or too few copies of the gene, alters theExtra or too few copies of the gene, alters the cell physiology.
Gene mutationsGene mutationsGene mutationsGene mutations• Point mutations are single base pair g pchanges. –Substitution –DeletionAddi i–Addition
b i i iBase substitution mutations• Transition mutations result from theTransition mutations result from the exchange of one purine, or pyrimidine, for another purine or pyrimidineanother purine, or pyrimidine. • Transversion mutations result from the exchange of a purine for a pyrimidine orexchange of a purine for a pyrimidine or visa versa.
Effects of point mutationsEffects of point mutationsEffects of point mutationsEffects of point mutations• Nonsense mutationMi t ti• Missense mutation• Silent mutation
U A AU A A(Termination codon)NonsensemutationSilentmutationU C A(codon for serine)(codon for serine)U C UMissensemutation U C U(codon for serine)mutationC C A(codon for proline)C C A
Nonsense mutationNonsense mutationNonsense mutationNonsense mutation• A nonsense mutation creates a stop codonh i l i dwhere none previously existed.• This shortens the resulting protein, possibly remo ing essential regionsremoving essential regions.
MissenseMissense mutationmutationMissenseMissense mutationmutationi i h h d f h• A missense mutation changes the code of the mRNA.• If AGU is changed to AGA the protein will haveIf AGU is changed to AGA, the protein will have an arginine instead of serine.• This may alter the shape or properties of the protein.
Silent mutationsSilent mutationsSilent mutationsSilent mutations• A silent mutation has no effect on protein sequence.• If an AGU was changed to an AGC, the ld ll h hprotein would still have the appropriate serine at that position.
FrameFrame‐‐shift mutations.shift mutations.Deletions or insertions of oneDeletions or insertions of one or two bases
FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.• Deletions or insertions of any number of bases from the coding sequence of the gene g q gwill alter the reading frame.• Deletion or insertion of three bases or multiples of three will omit or add an amino acids.acids.
FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.• For example, given the coding sequence and its corresponding protein : p g pAGA UCG ACG UUA AGCAGA UCG ACG UUA AGCA S Th L SArg ‐ Ser ‐ Thr ‐ Leu ‐ Ser
FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.•• The insertion of a The insertion of a CC base pair between bases base pair between bases 6 6 and and 7 7 would result in the following new would result in the following new ggcode.code.AGAAGA UCGUCG CCACAC GUUGUU AAGAAG CCAGAAGA UCGUCG CCACAC GUUGUU AAGAAG CCArgArg SerSer HisHis ValVal LysLysArg Arg ‐‐ Ser Ser ‐‐ His His ‐‐ Val Val ‐‐ LysLys
Addition of baseRNAmRNAU C A U C C U A U G G C U 3’‐End5’‐EndSer Tyr GlyAddition of USerUU C A C C U A U G G C U 3’‐End5’‐EndSer Pro Met AlaDeletion of CC’ dSerU C A C U A U G G C ULeu Trp5’‐End 3’‐EndDeletion of base
FrameFrame shift mutationsshift mutationsFrameFrame‐‐shift mutations.shift mutations.• Amino acids beyond the insertion point will be changed, producing altered non functional protein• The frame shift may generate a stop codon which ld t l d th t iwould prematurely end the protein.
Suppressor mutationsSuppressor mutations• Is a mutation that occurs in the anticodonregions of tRNA molecules.• Mutated tRNA are capable of decoding altered• Mutated tRNA are capable of decoding altered codons, therefore, suppress the effects of t ti i th t i dimutations in the protein‐coding genes.
Mutations are beneficial !Mutations are beneficial !• Provide a mechanism of change at the DNA levelOf l i b fi i l d• Often result in beneficial new genes and functions.E bl th i t d t t h i• Enable the organism to adapt to a changing environment.