1. Higher Human Biology Unit 1 – Human Cells
Section 4 – Mutation

2. Mutations – What do you remember?
What are the three effects that can result from a mutation?
Where does the mutation have to occur to pass onto the offspring?
Mutations result in variation within a species. Why is this a good thing?
Neutral, advantageous and disadvantageous
During meiosis, when the sex cells are produced
The mutation might give an advantage that will allow natural selection to select against.

3. a – Mutations We will be learning… State the definition of a mutation
Describe how a mutation can result in no protein or an altered protein being synthesised

4. What is a Mutation
A mutation is a change in the structure or composition of the organisms genome.
They occur randomly, spontaneously and at a low frequency.
Depending on the type and location of the mutation, the resulting protein may not function properly or not be expressed at all.
If the change in the genotype is expressed in the phenotype then the individual is called a mutant

5. Mutagens
Mutagenic agents can artificially increase the rate of mutations.
These mutations are called induced.
Mutagenic agents include: mustard gas, gamma rays, high temperatures, nuclear bombs/power and UV light.

7. Experiment into UV radiation on UV sensitive yeast

8. b – Single Gene Mutations
We will be learning…
To describe the single gene mutation which involves the alteration of a DNA nucleotide sequence as a result of substitution of nucleotides
To explain and identify nucleotide substitutions as missense, nonsense and splice-site mutations
To describe the single gene mutation which involved the alteration of a DNA nucleotide sequence as a result of insertion of nucleotides
To describe the single gene mutation which involved the alteration of a DNA nucleotide sequence as a result of deletion of nucleotides
To state that nucleotide insertions or deletions results in frame-shift mutations

9. Single Gene Mutations
These involve changes in one nucleotide e.g. deletion, insertion and substitution.
Since only one nucleotide is altered these changes result in minor changes to the organism.
Substitutions – Missense, Nonsense and Splice-Site mutations
Insertion and Deletion – Frame-Shift Mutations

11. Nucleotide Substitution
These can result three possible outcomes:
Missense Mutations – one amino acid being changed for another. This may result in a non-functional protein or have little effect on the protein.
Nonsense Mutations – result in a premature stop codon being produced which results in a shorter protein
Splice-site Mutations – result in some introns being retained and/or some exons not being included in the mature transcript.

12. Substitution – Missense – Replace a Base
Single-nucleotide substitutions include: missense (replacing one amino acid codon with another).
e.g.
Sickle cell disease
PKU

13. Missense Mutation – Sickle-Cell Disease
This is a blood disorder where the red blood cells change shape into an abnormal, rigid sickle shape.
This causes problems such as blocking blood vessels.
Symptoms – delayed growth, fatigue, shorter life, infections, jaundice
Advantages – protects against malaria
Mutation occurs on chromosome 11

14. Missense Mutation – Phenylketonuria (PKU)
Mutation occurs on chromosome 12
Phenylalanine and tyrosine are amino acids we obtain from protein in our diet
Usually, phenylalanine is converted, by enzyme action, to tyrosine
Tyrosine is converted to melanin (skin pigment)
With PKU phenylalanine is not converted to tyrosine
It accumulates and some of it is converted to toxins – brain fails to develop properly
New born babies are screened and, if they have the condition, are placed on a diet containing minimum phenylalanine

15. Substitution – Non-Sense – Replace a Base
Single-nucleotide substitutions include: non-sense (replacing one amino acid codon with a premature stop codon). Protein synthesis halted prematurely and results in the formation of a polypeptide chain that is shorter than normal and unable to function
E.g.
Duchenne Muscular Dystrophy

16. Nonsense Mutation – Duchenne Muscular Dystrophy
Caused by a mutation on the X chromosome such as a nonsense mutation
Affected gene fails to code for dystrophin, necessary for normal functioning of muscles – strengthens skeletal and cardiac muscle
Skeletal muscles become weak
Progressive loss of co-ordination
DMD is a muscle wasting disease

17. Do you remember what splicing is?
Splice-Site Mutation
Do you remember what splicing is?
DNA
Exon
Intron
Exon
Intron
Exon
Transcription
Splicing is the post transcription and pre- translational of mRNA ; removing introns and exons joined together (primary to mature mRNA), then using certain exons (alternative splicing)
Splicing is controlled by a specific nucleotide sequence at the splice site on introns which flank (beside) exons. Mutation occurs here.
E.g. Beta (β) Thalassemia
Primary
mRNA
Processing
Mature
mRNA
Translation
Protein

18. Splice-Site Mutation
Splice-site mutations (creating or destroying the codons for exon-intron splicing).
Diseases caused by splice-site - Beta (β) thalassemia
Destroying codon
Creating codon
DNA
Exon 1
Intron
Exon 2
Intron
Exon 3
DNA
Exon 1
Intron
Exon 2
Intron
Exon 3
Altered
mRNA
Exon 1
Exon 2
Exon 3
Altered
mRNA
Exon 1
Exon 3

19. Splice-Site Mutation – Beta Thalassemia
Caused by a mutation on chromosome 11
Sufferers have an excess of alpha globulin in their bloodstream
This damages the red blood cells
Many patients require blood transfusions as the are either mildly or severely anaemic.

20. Frameshift Mutations – (insertion and deletion)
If a base is inserted or deleted this leads to a frameshift mutation Every codon and amino acid coded for is altered from the point where the insertion or deletion has happened Insertion and deletion lead to large portion of the gene’s DNA to be misread. The protein that is produced differs from the normal protein by many amino acids and is usually dysfunctional.

21. Examples of diseases – Cystic Fibrosis
Deletion
Nucleotide deletion of a nucleotide sequence is the removal of bases, causing a frame shift
Examples of diseases – Cystic Fibrosis

22. Deletion – Frame-Shift Mutation Cystic Fibrosis
Three base-pair deletion on chromosome 7
A non-functioning protein is produced
Normally it is a membrane protein, that assists the transport of chlorine ions into and out of cells, that is coded for
In the absence of this protein a high concentration of chloride gathers outside cells
This causes mucus to become thicker and stickier
Lungs, pancreas and alimentary canal becomes congested and blocked

23. Results in extra copies of amino acid/ or fails to express (silenced)
Insertion
Nucleotide insertions or an expansion of a nucleotide sequence repeat (essentially insertion of a large number of copies of the nucleotide sequence).
Results in extra copies of amino acid/ or fails to express (silenced)
Examples of repeat expansion disease;
Tay-Sachs syndrome

24. Insertion – Frame-Shift Mutation Tay - Sachs Disease
Recessive chromosome 15 disease that affects the nervous system.
Body lacks hexosaminidase A (protein which breaks down chemicals in ganglioside, fatty substance GM2, thus builds up and prevents nerve functioning)
Slow development at 6 month
Loss of movement/ vision/hearing
Most die by 5yrs old

25. c – Chromosome Structure Mutations
We will be learning…
To define chromosome structure mutations – duplication, deletion, inversion and translocation.
To state that substantial changes in chromosome mutations often make them lethal

26. Now try these: What are the types of gene mutations?
Substitution, insertion and deletion
What are the types of gene mutations?
Which types do you think will have the greatest affect on the organism – explain/justify why.
Which type of
mutations are
these;
Insertion/deletion – because they cause a frameshift
Insertion
Insertion – 1, deletion – 2, substitution – 3
Deletion
Substitution

27. Chromosome Structure Mutations
Chromosome mutations are changes in the order or number of whole genes within a chromosome. This type of mutation involves the breakage of one or more chromosomes- the broken end is ‘sticky’ and can join to another broken end
There are four different types of chromosome mutation
Duplication – this is where a section of a chromosome is added from its homologous partner
Deletion - this is where a section of a chromosome is removed
Inversion – this is where a section of chromosome is reversed
Translocation – this is where a section of a chromosome is added to a chromosome, not its homologous partner

29. Duplication Chromosome Mutation
A section of a chromosome replicates itself so that a set of genes is repeated.
Normal
section
A B C D
E F G
E F G
H I J K L
Mutant
section
A B C D
E F G
E F G
H I J K L
Duplicated genes
There are a number of causes for duplication but a common cause is known as ‘Replication Slippage’
Replication slippage happens during the DNA replication process when the polymerase accidentally detaches from the strand and replication stalls.
When polymerase reattaches to the DNA strand, it starts the copying process at the wrong position and accidentally copies the same section more than once..

30. Duplication A B A C B D C E D F E F G G H H Duplicated Genes from
New chromosome A B C D E F G H
Duplicated
Genes from
Homologous
chromosome A B C D E F G H
BREAK
Original chromosome

31. Deletion Chromosome Mutation
A chromosome may break in two places and the section in between lost during the repair with the result that the organism loses a number of genes
Normal
section
Deletion normally has a drastic effect as the ‘shorter’ chromosome lacks certain genes
A B C D
E F G
H I J K L
Break
Break
Mutant section
A B C D
Deleted section

32. Deletion A A B B C C G D New chromosome H E F G H BREAK D E F
Original chromosome D E F
Deleted genes

33. Deletion Chromosome Mutation Cri-du-Chat Syndrome
Deletion of part of the short arm of chromosome 5
"Cri du chat" is French for "cry of the cat". The infants cry sounds like a cat.
Most cases of cri du chat syndrome are not inherited. The chromosomal deletion usually occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early foetal development. People with cri du chat typically have no history of the condition in their family.

34. Inversion Chromosome Mutation
Inversions involve the breakage of a segment on a chromosome which is then reversed and reattached. This mutation changes the arrangement of genes.

35. Inversion Chromosome Mutation Haemophilia A
This involves a rearrangement of genetic material called an inversion.
This cases mutated coagulation Factor 8. Clotting factors work to clot our blood to stop the flow.
Symptoms vary in severity e.g. deep internal bleeding, easy bruising and joint damage.

36. Translocation Chromosome Mutation
In this case a piece of one chromosome breaks off and joins onto another non-homologous chromosome e.g. a chromosome that is not its matching partner
chromosome 1
chromosome 2
normal
A B C D
E F G
U V W X
normal
mutant
mutant
two pieces of chromosome join here
Problems occur during pairing of homologous chromosomes. Gametes formed are often not viable. Translocation is a second less common reason for Down Syndrome compared to trisomy ( 3 chromosomes on 21)

37. Translocation A A B B C C D D E E S Chromosome 1 T Translocated genesU V A B C D E S T
Translocated genes A B C D E S T U V
Chromosome 1
Chromosome 2
BREAK

38. Translocation Chromosome Mutation Familial Down’s Syndrome
in 5% of cases one parent has the majority of chromosome 21 translocated to chromosome 14
In people with Down's syndrome, all or some of the cells in their bodies contain 47 chromosomes, as there is an extra copy of chromosome 21. The additional genetic material causes physical and developmental characteristics associated with Down's syndrome.

39. Translocation Chromosome Mutation Chronic Myeloid Leukaemia
Reciprocal translocation of a gene from chromosome 22 fused with a gene on chromosome 9. This is a form of cancer where the protein produced promotes uncontrolled cell growth.
The image above shows a blood sample from a patient with CML with many more white cells than normal

40. Conclusion How frequent are mutations? (1) What is a mutant? (1)
Random, spontaneous at low frequency
How frequent are mutations? (1)
What is a mutant? (1)
Name 4 mutagenic agents.(4)
Name and describe 2 chromosome mutations.(4)
Explain the difference between a chromosome mutation and a gene mutation
Using a sample chromosome with genes labelled A-H show how each type of chromosome mutation changes the original chromosome
a change in the structure or composition of the organisms genome.
mustard gas, gamma rays, high temperatures, nuclear bombs/power and UV light.
Duplication, deletion, translocation & inversion
Gene mutation is a change in the nucleotide sequence, in a particular gene, whereas chromosomal mutation is a change in several genes, in the chromosome.

41. Now I can….. a State the definition of a mutation
Describe how a mutation can result in no protein or an altered protein being synthesised b
To describe the single gene mutation which involves the alteration of a DNA nucleotide sequence as a result of substitution of nucleotides
To explain and identify nucleotide substitutions as missense, nonsense and splice-site mutations
To describe the single gene mutation which involved the alteration of a DNA nucleotide sequence as a result of insertion of nucleotides
To describe the single gene mutation which involved the alteration of a DNA nucleotide sequence as a result of deletion of nucleotides
To state that nucleotide insertions or deletions results in frame-shift mutations c
To define chromosome structure mutations – duplication, deletion, inversion and translocation.
To state that substantial changes in chromosome mutations often make them lethal

42. Word
Meaning
Mutation
change in structure/composition of genome
Frequency
arise spontaneously, at random and rarely
Mutagenic Agents
Mutagenic agents artificially increase the rate of mutation – resultant mutations are said to be induced e.g. mustard gas, X rays and UV light
Genetic Disorder
a condition/disease that is directly related to an individual’s genotype
Single Gene Mutation
alteration of a nucleotide sequence e.g. substitution, insertion or deletion
Substitution
single-gene mutation in which one nucleotide is replaced by another
Chromosome mutation
This type of mutation brings about a change in the number or sequence of genes in a chromosome
Insertion
single-gene mutation in which an additional nucleotide is placed into a sequence
Deletion
single-gene mutation involving removal of a nucleotide from a sequence
Missense
substitution mutation; a single nucleotide change results in a codon for different amino acid
Nonsense
substance mutation in which a codon is changed to a stop codon, shortening the resulting protein
Splice site
mutation at a point where coding and non-coding regions meet in a section of DNA

43. Word
Meaning
Frame shift
gene mutation in which all amino acids coded for after the mutation are affected
Duplication
chromosome mutation in which a sequence of genes is repeated on a chromosome
Translocation
chromosome mutation in which part of a chromosome becomes attached to another
Intron
non-coding sequence of DNA
Exon
sequence of DNA that codes for protein
Sickle Cell Disease
disease caused by a substitution mutation in the gene encoding haemoglobin
Haemophilia
inherited disease in which blood clotting fails or is very slow

44. CfE HH 2016 A Q2 D

45. CfE HH 2015 A Q4 D

46. Revised Higher 2014 A Q6 A

47. CfE HH 2017 B Q2

49. Suggested activities UV sensitive yeast Mind map
Poster of gene and chromosome mutations