Mutations

CfE Higher Human Biology

Unit 1: Human Cells

Higher Human Biology Course Specifications

Higher Human Biology Course Specifications

Learning intention

To understand the nature, impact and importance of mutations as follows: -

Success criteria: -

(a) Understand and explain what mutations are.

(b) Describe and explain single gene mutations and their

consequences

(c) Describe and explain chromosome structure mutations

and their consequences.

Knowledge from Nat 5 Biology

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A mutation is a ___(a)_____ change to genetic material. Mutations may be ___(b)_____, confer an advantage or a disadvantage to __(c)_______

Mutations are ____(d)______ and are the only source of new ___(e)_____

Environmental factors such as __(f)____ and ____(g)___, can increase the __(h)____ of mutations

Word Bank (two are not used)

Mutations (7 minutes)

Watch the video clip and try to answer these questions on a white board: -

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• What is a mutation?
• What can cause mutations?
• Note an effect of mutations.

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Mutations

What are mutations?

• Mutations are changes in the DNA…..

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Try to expand this definition.

Think: What cell processes have you learned about so far in higher human biology that would be affected by this change?

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Linking your learning

Mutations

Mutations are changes in the DNA that can result in no protein or an altered protein being synthesised.

Mutations Bozeman science - gene mutations (6mins)

Watch and note some causes and effects of gene mutations

Causes of mutations

1. Error in copying the DNA sequence during cell division.

2. External factors

Anything in the environment that can cause a mutation is known as a mutagen.

Mutation Investigation

Investigating the effects of UV radiation on UV-sensitive yeast.

Optional

SSERC - Investigation Guide

Related Activity – Effect of UV radiation on UV-sensitive yeast cells. (p55-56 Higher Human bio textbook)

• What is the genetic difference between normal yeast cells and UV-sensitive yeast?

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• Why did the scientist do a series of dilutions of the yeast colony? Why could the scientist not just smear a colony directly from the petri-dish onto plates X and Y?

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• Plate Y was the control. What were they trying to prove with this control?

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• What’s the point in making UV-sensitive yeast? How can they be used in research?

Different types of mutations

https://www.youtube.com/watch?v=GieZ3pk9YVo

Gene, Chromosome and Chromosome Number Mutations

Two main types of mutations

• Single gene mutations

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• Chromosome structure mutations

Single gene mutations involve the alteration of a DNA nucleotide sequence as a result of:

• Substitution

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• Insertion

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• Deletion

1. Single gene mutation

Match the mutation to its description

Substitution

Insertion

Deletion

An additional nucleotide is inserted into the base sequence

One nucleotide is substituted for another in the base sequence

One nucleotide is deleted from the base sequence

(a) Substitution – one nucleotide is substituted for another in the base sequence , with no other nucleotides changing.

Met

Gln

Thr

Ser

STOP

Met

Ala

Asp

Ile

Leu

mRNA

mRNA

(b) Insertion – an additional nucleotide is inserted into the base sequence

Met

Gln

Thr

Ser

STOP

mRNA

Protein

Met

Gln

His

Leu

Protein

(c) Deletion – a nucleotide is deleted from the base sequence

Lys

mRNA

Growing polypeptide chain

Effects of frame-shift mutations

Frame-shift mutations (caused by insertion and deletion mutations) cause all of the codons and all of the amino acids after the mutation to be changed.

This has a major effect on the structure of the protein produced.

the big fox bit the dog but not the boy

1. Substitution - the "d" in dog got replaced by a "p". The sentence would now read:

the big fox bit the pog but not the boy

Whether a mutation like this will have an effect on the phenotype depends where in the gene it happens. It might not make any difference.

Pretend a sentence is a gene where each 3-letter word represents the triple base codons of DNA.

Take the sentence:

An analogy

3. Deletion – delete the o from fox (and keep all the words 3 letters long).

the big fxb itt hed ogb utn ott heb oy

2. Insertion – insert an r between the f and the o and keep the number of each word at three.

the big fro xbi tth edo gbu tno tth ebo y

More on substitution mutations

There are three possible effects of a substitution mutation. They are referred to by the following names:-

• Missense

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• Nonsense

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• Splice-site

1. Missense mutation

This results in one amino acid being changed for another.

This may result in a non-functional protein OR have little effect on the protein as there are more than one codon for many amino acids.

Missense mutations may not have any effect on the sequence of amino acids, however, sometimes it causes a major effect e.g. Sickle-cell anaemia

Example: Sickle-cell anaemia

Sickle cell anaemia has widespread symptoms.

2. Nonsense mutation

This results in a premature stop codon being produced which results in a shorter protein

Example: Duchenne muscular dystrophy

Muscular Dystrophy

https://www.youtube.com/watch?v=e2QfQ4Vce8A

This nonsense mutation affects the production of a protein called dystrophin which causes progressive muscle weakness and shortened life expectancy.

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It usually only affects boys.

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3. Splice-site mutation

This results in some introns being retained and /or some exons not being included in the mature transcript.

A different protein is therefore synthesised.

Thalassemia is a disease caused by a defect in haemoglobin synthesis and is caused by a splice site mutation.

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Intron

Exon

Normal splicing

Abnormal splicing

Example: Thalassemia

Example: Tay-Sachs disease (frameshift insertion)

Example: Cystic Fibrosis (frameshift deletion)

This frameshift mutation results in no production of a vital enzyme called hexosaminidase-A (Hex-A). Without Hex-A, a fat called GM2 ganglioside builds up in the nerve cells of the brain. Which results in progressive destruction of the nervous system.

This frameshift mutation affect the body’s ability to make the CFTR protein, which helps salt and water move into and out of cells. This causes the body to produce thick mucus, which affects the lungs and digestive system in particular. 

Most common cause of CF

Missense or Nonsense or Splice-site

(in this

case)

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Frameshift mutations

Summary of single gene mutations

Booklet Answers

• What are mutations?

2. Single gene mutations involve the alteration of a DNA nucleotide sequence. Name 3 types of single gene mutation

3. What is the effect of a missense nucleotide substitution mutation on a protein?

4. Describe a nonsense nucleotide substitution mutation.

5. Name the 2 single gene mutations which result in frameshift mutations

6. What effect do frameshift mutations have?

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Booklet Answers

• What are mutations?

Mutations are changes in the DNA that can result in no protein or an altered protein being synthesised

2. Single gene mutations involve the alteration of a DNA nucleotide sequence. Name 3 types of single gene mutation

Substitution, insertion or deletion of nucleotides

3. What is the effect of a missense nucleotide substitution mutation on a protein?

Result in a non-functional protein or have little effect on the protein

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4. Describe a nonsense nucleotide substitution mutation

Nonsense mutations result in a premature stop codon being produced which results in a shorter protein.

5. Name the 2 single gene mutations which result in frameshift mutations

Insertion and deletion

6. What effect do frameshift mutations have?

Cause all of the codons and all of the amino acids after the mutation to be changed. This has a major effect on the structure of the protein produced.

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7. The diagrams below show the base sequence for a section of a gene and a mutated version of this section. For each one, decide if this is an example of:

A: a deletion mutation

B: an insertion mutation

C: a substitution mutation

 Section of Gene CATGATTAACTT

Mutated version CATAGATTAACTT

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Section of Gene CATGATTAACTT

Mutated version CATGATTAATT

Section of Gene CATGATTAACTT

Mutated version CATGTTTAACTT

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B INSERTION

A DELETION

C SUBSTITUTION

Extended Response

Write notes on mutation under the following headings:

i) single gene mutations; 4

Select one of the diseases caused by gene mutation to find out more about the gene mutation that causes it, the symptoms and treatments. Be prepared to share you findings with others in the class.

Sickle cell anaemia, Thalassaemia, Tay-Sachs disease, Duchenne muscular dystrophy, Cystic fibrosis

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Extra

– what type of gene mutation causes PKU (phenylketonuria)

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• Gene mutations the basics
• Gene mutations activity

(in learning activities folder)

(in tray in bio store)

Single gene mutation activities

3. Diseases and gene mutations (Possible Homework Task)

Chromosome structure mutations

Involve the alteration to the structure of one or more chromosomes.

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Involves a change in the number OR sequence of genes on a chromosome.

Often occurs when chromosomes break and cross over during meiosis.

Watch Meiosis with crossing over (2 mins)

https://www.youtube.com/watch?v=SBqZvFVwtvA

Chromosome structure mutation

There are four types: -

• Deletion
• Duplication
• Inversion
• Translocation

break

deleted genes (lost)

rejoin

Deletion - where a section of a chromosome

is removed.

genes

break

segment from matching chromosome

Duplication - where a section of a chromosome is added from its homologous partner.

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Inversion - A broken chromosome segment is reversed and genes inserted back into the chromosome

break

rotate 180º

rejoin

break

translocated genes

join

Translocation - where a section of a chromosome is added to another chromosome, not its homologous partner.

Chromosome 1

Chromosome 2

Summary of chromosome

structural mutations

TASK – Use the cut out chromosomes to create versions of each chromosome mutation.

Genetic Disorder Research Task

Use the internet to identify a genetic condition that affects humans.

Create an information leaflet (through slides or docs) to inform people about the condition.

Within this leaflet should be:

• How common/rare is the condition?
• Which chromosome is affected and how.
• Is it dominant or recessive.
• What are the symptoms.
• What sort of treatment or care is available.
• Other facts that you think maybe relative.

This should be presented all in your own words and include pictures. It should include a list of references of where you got your information.

• Sickle Cell Anaemia
• Duchenne muscular dystrophy
• Cri-du-chat syndrome
• Haemophilia A
• Chronic myeloid leukaemia
• Thalassemia
• Tay-Sachs disease

e.g. Cri du chat syndrome

• Deletion of end of Chromosome 5
• Lower mental function and small head
• Crying sounds like a cat

Quick Questions!

Q1. Explain what is meant by a mutation?

Q2. An original base sequence of a gene is TTACGCTAC. Name the

mutations which cause the following sequence changes.

a) TACGCTAC b) TTACGGCTAC c) TGACGCTAC

Q3. Which of the mutations in Q2 are frameshift mutations?

Q4. Which mutation causes an early STOP codon to be inserted,

missense, nonsense or splice-site?

Q5. Which chromosome mutation causes a section of chromosome :-

a) to be added from a homologous partner?

b) to be added to a non-homologous partner?

Quick Questions!

Q1. Explain what is meant by a mutation?

A. changes in DNA/genes/chromosomes resulting in no OR altered protein

being synthesised.

Q2. An original base sequence of a gene is TTACGCTAC. Name the

mutations which cause the following sequence changes.

a) TACGCTAC b) TTACGGCTAC c) TGACGCTAC

A. a) deletion b) insertion c) substitution

Q3. Which of the mutations in Q2 are frameshift mutations?

A. a and b

Q4. Which mutation causes an early STOP codon to be inserted,

missense, nonsense or splice-site?

A. nonsense

Q5. Which chromosome mutation causes a section of chromosome :-

a) to be added from a homologous partner?

b) to be added to a non-homologous partner?

A. a) duplication b) translocation

Write notes on mutation under the following headings:

(i) Single gene mutations 5

(ii) Chromosome mutations 3

(8)

Essay time

3

Starter questions

Booklet Answers

• Which type of chromosome mutation involves

a section of a chromosome is added from its homologous partner?

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a section of chromosome being reversed?

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a section of a chromosome being removed?

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a section of a chromosome is added to a chromosome, not its homologous partner?

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2. Decide if the following statements are true or false. If you think it is false, correct the word underlined.

• A substitution mutation will change all of the amino acids after the mutation and will cause the protein to be non-functional.
• A missense mutation results from substitution of a nucleotide.
• A missense mutation involves a stop codon being produced early, resulting in a shorter protein.
• Single gene mutations involve the alteration of a DNA nucleotide sequence as a result of the substitution, insertion or duplication of nucleotides.
• In an inversion chromosome mutation, a section of a chromosome is added to a chromosome, not its homologous partner.

f) In a translocation chromosome mutation, a section of a chromosome is added from its non homologous partner.

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Booklet Answers

• Which type of chromosome mutation involves

a section of a chromosome is added from its homologous partner?

duplication

a section of chromosome being reversed?

inversion

a section of a chromosome being removed?

deletion

a section of a chromosome is added to a chromosome, not its homologous partner?

translocation

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2. Decide if the following statements are true or false. If you think it is false, correct the word underlined.

• A substitution frameshift mutation will change all of the amino acids after the mutation and will cause the protein to be non-functional.
• A missense mutation results from substitution of a nucleotide.
• A missense nonsense mutation involves a stop codon being produced early, resulting in a shorter protein.
• Single gene mutations involve the alteration of a DNA nucleotide sequence as a result of the substitution, insertion or duplication deletion of nucleotides.
• In an inversion duplication chromosome mutation, a section of a chromosome is added to a chromosome, not its homologous partner.

f) In a translocation chromosome mutation, a section of a chromosome is added from its non homologous partner.

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3. A chromosome mutation in humans can result in the formation of the Philadelphia chromosome, which is associated with a form of leukaemia. The stages leading to the formation of a Philadelphia chromosome are shown in the diagram.

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• Name the type of chromosome mutation, shown in the diagram, which results in the formation of a Philadelphia chromosome.

Translocation

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• The presence of a Philadelphia chromosome causes a form of leukaemia through the over-production of an enzyme. A drug has been used to successfully treat this form of leukaemia by binding at the active site of the enzyme.

The table shows the white blood cell counts from a patient with leukaemia before and after treatment with this drug.

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Calculate the percentage decrease in the number of white blood cells after treatment with this drug.

 (Change/start) x 100

Change: 150000 – 7500 =142 500

 149 925/150000 = 0.95

 0.95 x 100 = 95%

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Extended Response

Give an account of gene mutation under the following headings:

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• The occurrence of mutant alleles and the effect of mutagenic agents 3

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• Types of gene mutation and how they alter amino acid sequences 7

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Total=10

• Mutations are random/spontaneous/by chance
• Low frequency/rare
• Name one type of mutagenic agent e.g. chemicals, mustard gas.
• A second type of mutagenic agent e.g. radiation, UV light, x-rays etc.

Max 3 marks.

• Gene mutations are random changes in DNA sequences/genes/alleles the genome.
• Gene mutation name AND description; substitution, insertion, deletion. Substitution – base/base pair/nucleotide is replaced/substituted by another.

Insertion – base/base pair/nucleotide is added/inserted.

deletion – base/base pair/nucleotide is removed/deleted/

• Another gene mutation name and description
• If 2 or not awarded give 1 mark for all 3 names but no/incorrect descriptions.
• Mutations are important in evolution
• Insertion/deletion results in a frame shift mutation/expansion of the amino acid sequence.
• Substitutions result in missense, nonsense and splice site mutations.
• Missense is where the protein may carry out a different protein or not function
• Nonsense a premature stop codon is generated/shorter amino acid chain/protein may not function.

Max 7 marks

Starter question

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If it takes DNA polymerase one second to copy one nucleotide, how long will it take to copy a human genome consisting of 3 billion base pairs?

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Match the mutation to its description

(a) Substitution

(b) Insertion

(c) Deletion

(e) Splice site

(f) Nonsense

(d) Missense

1. A premature stop codon is produced.

6. Some introns may being retained /some exons not included in the mature mRNA.

2. An additional nucleotide is inserted into the base sequence

3. One amino acid is changed for another.

4. One nucleotide is substituted for another in the base sequence

5. One nucleotide is deleted from the base sequence

The diagram represents the sequence of bases on part of one strand of a DNA molecule.

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The effect of a mutation on this strand of DNA is shown below.

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Which of the following words apply to this mutation?

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• Duplication
• Gene mutation
• Substitution
• Inversion

E. Frameshift

F. Missense

G. Deletion

H. Chromosome mutation

I. Translocation

J. Insertion