MutationsSBI 4U

November 23rd, 2012

What are Genetic Mutations?Changes in the DNA sequence caused by various

mechanismsMechanisms of change: synthetic chemicals, radiation,

incorrect replication, and random mutationsBeneficial vs. harmful

Genetic MutationsSmall ScaleLarge Scale

Small Scale MutationsSmall-scale mutations: mutations of an

individual base pair (point mutations) or of small groups of base pairs

3 types: -substitution-insertion/deletion-inversion

Point MutationsMutations of an individual base pair3 Types:Substitution of one base for anotherInsertion or deletion of a single base pairInversion of two adjoining base pairs

Effects of small-scale mutations can range from being positive to none to severe!

Small-Scale MutationsCan be functionally divided into 4 categories:Missense mutationsNonsense mutationsSilent mutationsFrameshift mutations

Missense MutationMissense mutation: when a change of a single base pair or

group of base pairs results in the code for a difference amino acidMay be non-functional or functional (differently)

Missense MutationEx: sickle cell diseaseHemoglobin molecule altered – sickle shape

of RBCsReplacement of A by T – makes valine instead

of glutamic acid

Nonsense MutationNonsense Mutation: occurs when the change of

a single base pair or group of base pairs results in a premature stop code in the gene

Unable to function

Nonsense MutationEx: Cystic fibrosisOnly 493 amino acids produced instead of

1480 (in some cases)

Silent MutationSilent mutation: occurs when the change in

one or more base pairs does not affect the functioning of the gene.

Resulting protein not altered!

Frameshift MutationFrameshift mutation: occurs when one or more nucleotides

are inserted into or deleted from a DNA sequence, causing the reading frame of codons to shift in one direction or the other

Multiple missense and nonsense mutationsEx: Tay Sachs disease

Large-Scale MutationsLarge-scale mutations involve multiple

nucleotides, entire genes, or whole regions of chromosomes

Entire coding regions of DNA may be removed – ex: Dystrophin and Duchenne muscular dystrophy

Large-Scale MutationsChromosomal translocation: entire genes

or groups are moved from one chromosome to another

Inversion: reversal of direction in the genome

Trinucleotide repeats triplet of nucleotides repeat uncontrollably - - CAG CAG CAG CAG CAG

Ex: Huntington’s disease

Causes of MutationsSpontaneous: arise from inaccurate DNA

replicationInduced: environmentally caused

Induced MutationsCaused by a mutagen, that directly alters

the DNA within a cell2 types of mutagens: chemicals and radiation

Chemical MutagensAny chemical agent that can enter cell

nucleus and chemically alter the structure of the DNA

Ex: tobacco smoke and exhaust fumes

Chemical MutagensHow do they cause mutations? Some mimic a

DNA nucleotide. Ex: ethidium bromide inserts itself between the strands of the double helix and alters structure of DNA

RadiationLower energy radiation such as ultraviolet B

can cause bonds to form between adjacent nucleotides – making a kink - - ex: skin cancer

Higher energy radiation – breaks bonds within the DNA molecule re-arrangement or deletion of large portions of chromosomes. Ex: x-rays can lead to tumours