PREPARE BY: MISS LOCK SHU PING

CHAPTER 7.0: MUTATION

Mutation

MUTATION CLASSIFICATION

AND TYPES

GENE MUTATION

CHROMOSOMAL MUTATION

1.Explain mutation2.Classify mutation into ‘gene

mutation’ and ‘chromosomal mutation’.

3.State the types of mutation4.Define mutagen5.State types of mutagen

MUTATION ?

A permanent change in the amount, arrangement or structure of the DNA of an organism which can passed down to the next generation.

WHAT IS MUTATION?

‘Changes in the genetic material (genes or

chromosomes) of a cell’Can be inherited if mutation occurs in reproductive cells during formation of

gametes

Types of mutation

- mutations that cause by mutagen

- e.g: exposure to mutagen

- mistakes happen spontaneously during DNA replication, DNA repair, or DNA recombination.

- e.g: nondisjunction during meiosis

( details will be explain in 16.3)

Based on the cause

Spontaneous mutation Induced mutation

Spontaneous Mutation

mistakes happen spontaneously during DNA replication, DNA repair, or DNA recombination.

Induced Mutation

Mutations that cause by mutagen

A variety of agents increase the frequency of

mutation

- Physical and chemical agents that induces changes in DNA

Physical agent:Ultraviolet rayIonizing radiation (X-ray, gamma ray, alpha particles, neutron and electron)

Chemical agent:Mustard gas, nitrous acid, base analogue etc.Colchicine , ethidium bromide

Physical agentPhysical agent EffectIonizing radiation • -breaks in one or both

strands (can lead to rearrangements, deletions, chromosome loss, death if unrepaired; this is from stimulation of recombination)

• -damage to/loss of bases (mutations)

• -crosslinking of DNA to itself or proteins

UV radiation pyrimidine dimers in DNA

Chemical agentChemical agent Effectnitrous acid- It causes C to U, meC to

T, and A to hypoxanthine deaminations.

ethyl methanesulfonate mutagenic and recombinogenic, or mispair to result in mutations upon DNA replication.

Colchicine Prevent the formation of spindle fibre

Shortwave UV (UVA) Causes Thymidine Dimers

Mutation that causes by agent orange .

About 500 000 children in Vietnam born with birth defects during Vietnam war

Mutant • A mutated gene, alternatively,

• An organism carrying a gene that has undergone a mutation that

• shows new phenotype traits as a result from mutation

New phenotypes traits showed by this children as a result of mutation

GeneticMutation

1. Base substitution

2. Base insertions3. Base deletions4. Base inversion

Chromosomal Mutation

1. Structural change / Chromosome Aberration

2. Alterations of chromosome number

Aneuploidy Euploidy /

Polyploidy

Mutation classificationBy effect on structure

of gene (involve small scale mutation)

of chromosome (involve large scale mutation)

Genetic Mutation

Chromosomal Mutation

Mutation

Base substitutionBase insertionsBase deletionsBase inversion

1.Explain gene mutation2.Classified gene mutation3.Describe base substitution as point

mutation4.Explain frameshift mutation5.Descibe base insertion as a frameshift

mutation6.Describe base deletion as a frameshift

mutation

16.2 Gene Mutation/ Point Mutation

• A type of mutation which involved• A change in the nucleotide sequence of the DNA

within a gene

change the amino acid sequence and thus, changes

the proteinDifferent protein produced as the effect of mutation may not function as normal

Example : sickle cell anemia

change the amino acid sequence

changes the protein

Change the DNA nucleotide sequence

AGCTTA

TCGAAT

AGCGTTA

TCGCAAT

AGCGTA

TCGCAT

AGCTA

TCGAT

AGTCTA

TCAGAT

Normal

DeletionSubstitutionInsertion Inversion

Gene Mutation

Classification of gene mutation• Base substitution – one or a few base pairs in the

nucleotide sequences in genes is substitute (replaced)

• Base insertions – addition of 1 or a few base pairs in the nucleotide sequences in genes

• Base deletions – loss of 1 or a few base pairs in nucleotide sequences

• Base inversion – 2 base pairs or more are inverted in nucleotide sequence

• Base Substitution :

• Base Insertion:

THE FAT CAT ATE THE RATTHE FAT CAR ATE THE RAT

THE FAT CAT ATE THE RATTHE FAT CAT CAT ETH ERA

• Base Deletion :

• Base Inversion :

THE FAT CAT ATE THE RATTHE ATC ATA TET HER AT

THE FAT CAT ATE THE RATTHE FAT CAT ATE THE TAR

Analogy that can be made to show point mutation

AGCGTA

TCGCAT

AGCTA

TCGAT

AGTCTA

TCAGAT

AGCGTTA

TCGCAAT

AGCTTA

TCGAAT

Normal DeletionSubstitutionInsertionInversion

• one or a few base pairs in the nucleotide sequences in genes is replaced with another base pairs.

• Can cause changes in base sequence – results in changes of codon . E.g: (UAU change to UGU)

• 1 codon = 3 base/ nucleic acid (coding for 1 amino acid)

CAC-AAG-UAU-CAC-UAA

his lys tyr his stop

CAC-AAG-UGU-CAC-UAA

his lys cys his stop

Before mutation

Substitution mutation

Point Mutationa type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA.

Changes in codon:

Leads to amino acid changesThe altered codon codes for different amino acid

Changes a codon to stop codon (UAG / UAA / UGA ) Leading to a nonfunctional protein

Missense mutation nonsense mutation

Changes in codon

Nonsense

Mutation changes a

codon to stop codon

Leading to a nonfunctional protein

Changes in codon

Leads to amino acid changes

the altered codon codes for an amino acid that is not the right sense.

Missense

Mutations

Changes in codonSilent

Mutations have no effect on

the encoded protein.

a change in a base pair transform one codon into another that translated into the same amino acid.

happens because of redundancy in the genetic code.

AGU AGCSER SER

Silent Mutatio

ns

Changes in codon:

Leads to amino acid changesThe altered codon codes for different amino acid

Changes a codon to stop codon (UAG / UAA / UGA ) Leading to a nonfunctional protein

Missense mutation nonsense mutation

Base substitutionCAC-AAG-UAU-CAC-UAA his lys tyr his stop

CAC-AAG-UGU-CAC-UAA his lys cys his stop

CAC-AAG-UAG his lys stop

Before mutation

Missense mutation

Nonsense mutation

Differences between missense and nonsense mutation is missense mutation altered codon codes for different amino acid while nonsense mutation alteres codon to stop codon.

EFFECT OF BASE SUBSTITUTION

Sickle cell Anemia

SICKLE-CELL ANEMIA

Missense mutation

Defective red blood cell

Abnormal Hb – Sickle (S) shape

Hb ~ 4 polypeptide chain

(2- & 2-)

Encode by different gene

HOW SICKLE-CELL ANEMIA HAPPEN?

Happens because substitution mutation

Amino acid valine replaces glutamic acid at a single position in the protein (-strand)

Patient suffer from anemia ~ Hb-S stiff & tend to accumulate in small capillary

Hb is not efficient of transporting

oxygen

Missense mutation

Sickle cell Anemia• abnormal haemoglobin crystallizes &

erythrocyte is pulled into a sickle shape• the cells fragment easily or clump

together to clog the capillaries (and less O2 is transported)

TRY THIS…

A. GGCATT

B. GGCCATT

C. GGCTT

D. GCGCTT

State what type of gene mutation below:

Normal DNA : GGCCTT

GGCATT BASE SUBSTITUTION

GGCCATT BASE INSERTION

GGCTT BASE DELETION

GCGCTT BASE INVERSION

WHAT ARE THE DIFFERENCES BETWEEN MISSENSE AND NONSENSE MUTATIO N?

Missense mutation

altered codon codes

for different amino acid

nonsense mutation

altered codon to

STOP codon.(UAG / UAA /

UGA )

What is the genetic disorder shown above?

Sickle- cell anemia

What type of gene mutation that cause this genetic disorder to happen? Why?

Because of substitution mutation. Amino acid valine is replaced by glutamic acid at a

single position in the protein (-strand)

Point Mutations in Coding Sequences

Missense – changes amino acid Nonsense – creates stop codon

Frameshift – alters remainder of reading frame results in completely different amino acid sequence.

FRAME-SHIFT MUTATIONS

• Involve insertion/deletion of a base pair or more into the nucleotides sequence of DNA

• Many of these deletions/insertion start in the middle of a codon

• Shifting the reading frame by one or two bases • Frame shift mutations cause the gene to be

read in the WRONG three base groups (codon)

Example

Insertion of U base

Change the sequence of amino acids

Deletion of C base

Resulting in stop codon-no further

amino acid produces

• From the mutation point, it abrupts the coding sequence of amino acid. Changes in codons results in changes in amino acids

• All the nucleotides downstream of the deletion/ insertion will be improperly grouped into codons.

different polypeptide is produced.

Frame-shift Mutations

• The result will be – extensive missense, ending sooner or – later in nonsense - premature termination.

• Effect ~ usually harmful to human• e.g: Major thalasemia (mutant

homozygote alleles)

A C A C G C A C U C C C

Amino acid 1

Amino acid 2

Amino acid 3

Amino acid 4

Codon 1

Reading frame in mRNAFrame-shift Mutations

Normal

Mutant A C A C G C A C U C C C

Codon 2 Codon 3 Codon 4

Codon 1 Codon 2 Codon 3

Amino acid 1

Amino acid 2

Amino acid 3

Reading frame is shift one base infront

FRAMESHIFT MUTATION

Nonsense

Non frameshift

Extensive missense

• Additions of nucleotide pairs in a gene• All the nucleotides that downstream of the

insertion will improperly group into codons.• Analogy:THE FAT CAT ATE THE RATTHE FAT CAT CAT ETH ERA

insertion improperly group into codons

Extensive missense

• Losses of nucleotide pairs in a gene• All the nucleotides that downstream of the

deletion will improperly group into codons.• Analogy:

– THE FAT CAT ATE THE RAT– THE ATC ATA TET HER AT

improperly group into codons

Extensive missense

• Eg. of disorder due to base deletion is thalasemia– deletion of nucleotide base pairs for

genes which – control the production of Hb α and β

chains– major thalassemia causes serious

anaemia

• 2 base pairs or more in nucleotide sequence are inverted

• Change the codons => changes in amino acid

• Usually the effect is minor phenotype abnormality

• Normal code: AGA-GTC-TTC ser glu lys

• Base inversion: AGA-TGC-TTC ser thr lys

Base Substituti

on

Base Insertion

Base Deletion

Base Invertion

Genetic Mutation

Chromosomal Mutation

Mutation

Chromosome aberration

Alterations in chromosome

number

1.Explain chromosomal mutation

2.Classify chromosomal mutation into chromosomal aberration and chromosomal number alteration .

3.Explain chromosomal aberration

4.State and describe types of chromosomal aberration

Chromosomal Mutation

Chromosomal MutationDefinition:

• Abnormalities ~ in chromosomal structure (chromosome aberration) & changes in chromosome number (aneuploidy / euploidy)

Types of chromosome mutation

Chromosome aberration

Alterations in chromosome

number

Euploidy(Polyploidy)

Aneuploidy

DeletionInversion

Translocation

Duplication

Structural change

Chromosome Aberration• Involving the breakage of chromosome

and rearrangement a certain segment or parts of chromosome

• 4 types : DeletionInversion

Translocation

Duplication

DELETION

ChromosomalMutations:

DELETION

DUPLICATION

ChromosomalMutations:

DELETION

DUPLICATION

INVERSION

ChromosomalMutations:

DELETION

DUPLICATION

INVERSION

TRANSLOCATION

ChromosomalMutations:

the lost of 1 segment containing 1 or more genes

ABCDEFGHI

Break off

Break off

ABC

GHI

DE

F

ABCGHI

Losing middle section

Deletion

Example: Cri-du-chat syndrome

1.due to deletion of a section of the short arm of chromosome 5

2.characteristics:• small head• unusual facial features• mentally retarded• cries like the mew of a cat

3. Usually dies in infancy/ early childhood

krē-du̇-ˈshä-

Example: Cri-du-chat syndrome

• small head• unusual facial features• mentally retarded• cries like the mew of a cat

a region of a chromosome breaks off and rotates through 180° before rejoining the chromosome

ABCDEFGHI

break

off

break

off

ABCFEDGHI

ABC

GHI

DEF

Inversion

Centromere lies within inverted

region

Centromere lies outside inverted

region

Inversion

Inversion

Involves a region of a chromosome breaking off and rejoining either the other end of the same chromosome or another non-homologous chromosome

Translocation

A B C D E F G H I chromosome 1

M N O P Q R S chromosome 2

A B P Q R S

F G H IC D EN OMreciprocal

translocation

• Most common: RECIPROCAL TRANSLOCATION[ 2 non-homologous chromosomes exchange fragments ]

• In non-reciprocal translocation, a chromosome transfers a fragment without receiving any in return

• Example: Robertsonian translocation

• Robertsonian translocation involves breaks at the extremes ends of the short arms of two nonhomologous chromosomes (13,14,15, 21 and 22).

a region of a chromosome becomes duplicated; an additional set of genes exists

ABCDEFGHI Additional

set of genes

ABCDEFGHIFGHI

Duplication

Differences between chromosomal mutation and gene/point mutation

Chromosomal mutation Gene/point mutation

A process that cause changes in chromosome structure or number

A process that causes changes in the base sequence of the DNA

Types of chromosomal mutation are chromosomal aberration and alteration in chromosome number.

Types of gene mutation are base substitution, base inversion, base deletion and base insertion.

No frameshift mutation Base deletion and base insertion cause frameshift mutation

No production of non-functional protein

Leads to production of non-functional protein

1. The DNA nucleotide base sequence can be altered in several ways.Which of the following is NOT involved in gene mutation?

A. SubstitutionB. InversionC.DeletionD.Translocation

The figure below shows a pair of homologous chromosomes during prophase I.

What could have cause this?

A B C G H

A B C G H

D F

E

A.SubstitutionB.InversionC.DeletionD.Duplication

The figure shows two types of chromosomal mutations to the genetic sequence below.

A B C D E F G H

A B E D C F G H A B E F G H

I II

What are the processes that cause the chromosomal mutation I and II above?

I IIA Inversion DeletionB Inversion DuplicationC Deletion InversionD Translocation Deletion

Try this….Determine the types of mutation

shown in the figure below.Normal gene sequence ABCDE FGH(i) ABCE FGH(ii) ADCBE FGH(iii)ABCBCDE FGH(iv)ABCDE MNOPQ