1. MECHANISMS OF GENETIC CHANGE

2. GENETIC MUTATION
Mutations occur all the time in our cells and usually do not cause us any harm, particularly if the mutation takes place in a single somatic cell.
If the mutation takes place in a germ line cell then we have the chance of passing it on to our offspring, who will then have the mutation in all their somatic cells. Depending on the mutation, the results could be problematic.
Mutations can take place in whole chromosomes. Cells can have a different number of chromosomes due to non-disjunction or fertilization from 2 sperm - these can be seen easily under a light microscope.
Chromosomes can also exchange parts of themselves. In this case the same amount of genetic material is still present in the cell. Usually, when large enough sections of chromosomes exchange, this can also be seen under a light microscope.
Chromosome can also gain or loose sections.
DNA mutations in the base pairs cannot be seen with a microscope. The gene must be sequenced in order to identify the specific change.

3. CHROMOSOME MUTATION Change in number
Aneuploidy occurs when cells can contain the wrong number of chromosomes. They can have more or less chromosomes than their usual number. Trisomy 21 is an example of this.
Aneuploidy is quite common in somatic cells and does not have a negative effect on the person.
Aneuploidy in gametes can be devastating for the embryo that in most cases would not survive to term.
Polyploidy is when a cell contains one or more complete extra sets of chromosomes. Humans would therefore be 3N=69 or 4N=92.
When a change in number of chromosomes occurs, the number of copies of genes decreases or increases, but the genes themselves remain intact.

4. CHROMOSOME MUTATION Change in number
Triploidy – 3 copies of every chromosome.
Trisomy - 3 copies of one chromosome.

5. CHROMOSOME MUTATION Rearrangement
Other than the number of chromosomes being altered, the actual chromosomes themselves can be rearranged.
Parts of chromosomes can be deleted, duplicated or inverted.
Chromosomes can even exchange parts of their chromosome with other chromosomes. This is called a translocation.
In a translocation there is usually no addition or deletion of genetic material.
During a chromosome rearrangement a gene maybe interrupted.

6. CHROMOSOME MUTATION Rearrangement - deletion

7. CHROMOSOME MUTATION Rearrangement - duplicated

8. CHROMOSOME MUTATION Rearrangement - inversion

9. CHROMOSOME MUTATION Rearrangement - translocation
When part of one chromosome is translocated onto another chromosome there is a chance the function of a gene can be disrupted.
Here is a case study of a translocation between chromosome 9 and chromosome 22.
The breaks in this translocation happens to be in the 2% coding region.
A new gene is formed on chromosome 22 that causes a type of leukaemia.
The gene formed on chromosome 9 has no apparent harmful affect.
t(9;22)
Normal 22
Normal 9
t(9;22)
22q11
t(9;22)
Normal 22
9q34
Normal 9
t(9;22)

10. CHROMOSOME MUTATION Rearrangement - translocation
The abl gene on chromosome 9 has been translocated (moved) onto chromosome 22, right next to the bcr gene.
This makes a fusion of two genes that would not normally be together. It is called the bcr-abl fusion gene and it sits on chromosome 22.
100% of patients with this type of leukaemia have this gene rearrangement including the 5% who don’t have the chromosomal translocation.

11. CHROMOSOME MUTATION Rearrangement - translocation abl gene – Chr 9
bcr gene – Chr 22
BCR-ABL fusion gene
BCR-ABL protein

12. CHROMOSOME MUTATION
Rearrangement - translocation

13. CHROMOSOME MUTATION Rearrangement - translocation
Green probe shows bcr gene
Red probe shows abl gene
Larger orange spot shows fused bcr-abl probes

14. GENE MUTATION
Mutations can also take place in genes where the base sequence is changed due to substitution, addition or deletion of single bases.
Particular codons can also repeat themselves a number of times.
Base substitution affects only the triplet it takes place in. This may then affect one amino acid in a chain.
Base addition or deletion not only affects the triplet that it takes place in but every codon that follows. These are known as frameshift mutations and can be far more problematic than a substitution mutation.
Trinucleotide repeats include the addition or deletion of a large number of repeats. Huntingtons disease (a neurological disorder) becomes more severe the more repeats of CAG a person has.

15. GENE MUTATION Substitution mutation THE CAT SAT ON THE MAT
THE RAT SAT ON THE MAT
Frameshift mutation
THE CAT SAT ON THE MAT
THE ATS ATO NT HEM AT
THE CAT SAT ON THE MAT
THE SCA TSA TO NT HEM AT
Trinucleotide repeats
THE CAT SAT ON THE MAT
THE CAT SAT SAT SAT SAT SAT SAT SAT ON THE MAT

16. DNA REPAIR
Even though DNA has the ability to repair itself it is always better to prevent mutations in cells.
Avoiding pollutants (avoid smoke filled areas), UV radiation (slip slop slap) and x-rays (lead apron) where ever possible.
When something goes wrong and the base sequence is changed DNA does have a repair kit that can come to the rescue.
Certain enzymes can recognize a change in the DNA sequence and set a whole range of other enzymes into action.
Restriction enzymes can cut the DNA, DNA polymerase can fill in any gap and DNA lygase rejoins the DNA strands.
Mutations occuring in chromosomes cannot be repaired by the DNA.

17. DNA REPAIR

18. TRANSPOSABLE ELEMENTS
Transposable elements or transposons for short are sections of DNA that have the ability to move from one section of a chromosome to another.
Due to this wandering nature, they can insert themselves into genes and disrupt their function.
They are also nicknamed ‘jumping genes’.
Here the gene for kernel colour (light yellow) has been disrupted by a transposon so that a mutant red colour has been produced.
The stripped effect occurs due to the transposon moving away and allowing the gene to function normally again.
Many thin stripes occur when the transposon jumps in and out of the gene.

19. WHERE WILL IT ALL END?

20. References
[no author] [n.d.] Iconographie [Internet] retrieved form site August 2004.