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L8 Mutation

The document discusses gene mutations, defining mutations and polymorphisms, and explaining how mutations can arise from environmental factors or spontaneously. It outlines various types of mutations, including base substitutions, deletions, and insertions, and their potential effects on protein synthesis and disease. Additionally, it highlights the significance of mutations as disease markers and the implications of chromosomal mutations.

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1 views

L8 Mutation

The document discusses gene mutations, defining mutations and polymorphisms, and explaining how mutations can arise from environmental factors or spontaneously. It outlines various types of mutations, including base substitutions, deletions, and insertions, and their potential effects on protein synthesis and disease. Additionally, it highlights the significance of mutations as disease markers and the implications of chromosomal mutations.

Uploaded by

auoop141
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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Gene Mutation

The gene sequence is the arrangement of bases along


the DNA strand
(e.g., ATTCCGGATCTGCCATAACGCCATTAGCC).
This order provides the exact instructions to create a
particular protein that control a unique traits (‫)الصفات‬

If one a base changes (mutation) the traits may change


Gene mutations
Objectives
1. Define mutation & polymorphism
2. How a mutation may arise
3. Impact of germline & somatic mutations
4. Type of mutations & their potential effects
5. Mutations as disease marker
6. The various types of chromosomal mutations
Definitions
Mutation: a permanent change in arrangement,
number or sequence of nucleotides in a gene
(e.g., ATACGGATCTGCCATAACGCCATTAGCC)
Ranges from one nucleotide to a segment of a
chromosome
Gene x Gene x

A C
T-A―C-G
Definitions
Allele: An alternative form (sequence) of a gene
Allele a: ATACCGGATCTGCCATAACGCCATTAGCC (wild
type)
Allele b: ATCCCGGATCTGCCATAACGCCATTAGCC (Mutant
type) A
Allele a (T-A) = 70%
Gene x A C

C
Allele b (G-C) = 30%

• Polymorphism: presence of > 1 allele of a gene


in a population
• A polymorphic gene: with > 1 allele in a
Mutation: inherited or
acquired
. Hereditary (germline) mutation:

Permanent changes in
DNA in reproductive
cells (egg or sperm)
that LATER becomes
part of the DNA of all
cells of offspring
Mutation: inherited or
acquired

. Acquired (somatic) mutations:

Permanent changes
that arise within
individual cells &
accumulate throughout
a person's lifetime
How can a mutation
arise?
1. Environmental factors
(Exogenous)
 UV light
 nuclear radiation
 certain chemicals
Mutation
Can alter some bases
so they look like other
nucleotides
How can a mutation
arise?
2. Mutations arise spontaneously
(endogenous )
At low rates due to the chemical instability of bases
Tautomerism – Changing the position of H+ atom of a base
Deamination – Change of amine group to a keto group

Incorrect pairing during replication


Tautomeric shift – Changing the position of H+ atom of a base

Amino―imino (NH)
Keto―enol (OH)

Keto ― enol (OH) Amino ―imino (NH


How can a mutation
arise?
3. DNA Replication error:

DNA polymerase makes a mistake


(once every 109 bases )
Types of Mutations
1. Base substitution (point mutation, single nucleotide
polymorphism [SNP])
2. Deletion, loss of one or more nucleotides in a gene
3. Insertion, addition of one or more nucleotides
in a gene
Frameshift mutations:
Insertion/deletion mutations can disrupt the

reading frame (coding region) in mRNA


Reading frame of a gene

AUG CUU AAU GGC CCC GGU CCU CCC


5’

GGC 3’
aa1 aa2 aa3 aa4 aa5 aa6 aa7 aa8 aa9
(Met) 1, 2 or > 3 nucleotides
(NOT multiple of 3) will disrupt the reading frame
Base substitution
(point mutation)
Replacement of a single nucleotide with another
nucleotide

Transition
o purine (A) » purine (G) T-A C-G
o pyrimidine (T) » pyrimidine (C) C-G T-A
o Common, caused by deamination &
tautomerization
replication error
Base substitution (point mutation)

Transversion

o purine «» pyrimidine

T-A A-T
C-G G-C
o Despite the high possibility of occurrence, it is less
common
o less likely to result in amino acid change, commonly
persist as "silent mutaion" in populations
Point
mutation
Effects of mutations
Base substitution (point mutation)

Depends on position of affected base(s)


THE CAT SAW THE DOG

Change one letter


THE BAT SAW THE DOG

THE CAT SAW THE FOG

THE CAB SAW THE DOG


missense
Missense mutations
Causes insertion of incorrect amino acid. The
protein function depends on the inserted amino
acid

Cysteine
Tryptophan
Missense mutations
Sickle cell disease is caused by a mutation in the Beta gene on chr 11
Nonsense mutations
Causes premature terminate of protein synthesis,
the product is short and not function

Cysteine
Insertion/Deletion
(Frameshift mutations)
 Loss or gain of 1 or 2 nucleotides result in
misreading of affected codon and ones that
follow.
 Different or non-functional protein

A
Triplet repeat expansion
5’ 3’
(CAG glutamine)

A set of genetic diseases caused by


trinucleotide repeat expansion (increased
multiple of a particular codon)

Where trinucleotide repeats is > stable


threshold
Triplet repeat expansion
 Huntington (HTT) disease CAG, glutamine (11-34)
Neurodegenerative disease: affects muscle coordination
& cognitive ability
Huntingtin protein with abnormal
glutamine
repeats, damage brain’s cells
 Threshold repeat number for a
disease
 HTT gene chr4, CAG (11-34) ―disease―> (37-100)

 Myotonic dystrophy (Myotonin protein kinase)


 DMPK gene chr19, CTG (5-35, at the 3’end of the
gene)
Mutations on noncoding
regions
Base substitution
Single nucleotide polymorphism (SNP)

The most common genetic variations,


occurs 1:100 to 1:300 bp.

Allow associations between a disease


(phenotypes) & specific SNPs (Genotype)

Accelerated identification of disease


genes.
SNPs disease association studies
GENOTYPE
VARIATION Known SNP
5’ Disease causing gene 3’

PHENOTYPE
VARIATION
(Health/Disease)

Molecular Diagnostic Tests


Chromosome mutation
 loss or gain of chromosome fragments
Occur by crossing over at meiosis
 Deletions
 Duplication
 Inversion
 translocations

Lots of abnormalities, in most cases lethal


 Aneuploidy, loss or gain of whole
chromosomes
 Part of a chromosome is missing
 Caused by errors (chromosomal crossover) during
meiosis
 New chromosome lacks certain genes
d

• Genes in homologous chromosome


are
copied
• The new&genes
inserted
are displayed twice
• Can be advantageous as new genes are gained
The connection between genes break & the
order of these genes are reversed
Translocation

Chronic myeloid leukaemia (blood cancer)

• Parts of two nonhomologous chromosomes breaks &


binds to the other.
Reading
Introduction to genetics, A molcular
biology approach
Chapter 16
Pages 313-323

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