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GENE
MUTATION

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Second level
Third level

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M. Mansyur Romi
Dept. of Anatomy, Embryology &
Anthropology

Mutation:
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any heritable change in the nucleotide

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of genomic
DNA caused by a
replication
Second
level error or by a mutagen.
Third level
Fourth level
Mutagen
a chemical or physical agent
Fifth level
that can cause a mutation in a DNA
molecule

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Second level
Third level
Fourth level
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Type
ofMaster
mutations
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Where occur:
* Gametic
or germinal
mutation
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* Somatic
Second
level mutation

Third level

How
occur:
Fourth
level
Fifth level
* Spontaneous
mutation
* Induced mutation
* Directed (adaptive) mutation

Germinal Mutation

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Occurs in a cell that is destined to

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become an egg or sperm

Istotransmitted
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future generations

Second level

Somatic
Mutation
Fourth level

Third level

Occurs
Fifthin
levela body cell ( liver, bone

etc) not ancestral to gametes.

Can affect to phenotype of its carrier

Spontaneous Mutation
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Arise as a natural errors in replication that

evade proofreading function of the DNA
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textsynthesize
new
Second
level
polynucleotide
mismatches
levelfrom random thermal motions of
Third
Result
Fourth level
atoms
and molecules in and near the DNA
Fifth level
Small
portion and due to foreign chemicals
or radiation that get inside cells and near
the DNA

1. Error in replication

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Third level
Fourth level
Fifth level

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Mutation rate ( )

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The frequency of mutation expressed

Second
level
as the
number
of mutation per locus
Third level per generation
per gamete
Fourth level
8 : 1 error in every 10 8
E. coli ~ 1/10
Fifth level
replication
Humans ~ 1/106 1/105 : due to a
higher complexity of human
replication
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Induced Mutation
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Following exposure to an agent, a

mutagen
, known
to produce
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mutation
Second
level above the rate at which
they
occurs spontaneously.
Third level

Fourth level
Mutagens
:
Fifth level
Industrial chemicals, pesticides
Substances in waste landfills
Cigarette smoke components,
drugs
Radiation from atomic warfare &
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nuclear power industry, etc

2. Effect of mutagen

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Third level
Fourth level
Fifth level

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Directed (Adaptive)
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Arises not as a result of blind variation on the

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genetical level and consequent selection, but

Secondsort
levelof purposeful behavior of the
by some
Third level
cell as aFourth
whole
level
level
The cell is Fifth
able
to mutate favorably under
conditions that would select for that new trait
Contradicts the darwinian theory of evolution
and the central dogma of molecular biology
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Size of Material

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Point mutation

single nucleotide change not

visible under a microscope

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Broad mutation
microscopically
Second level visible aberration

Third level

mechanism:
Fourth level

deletion
Fifth level
insertion
substitution (transversion, transition) etc

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Third level
Fourth level
Fifth level

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Point mutation common

(single
site to
mutation)
: replace one
nucleotide
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with another

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Divided into two categories:
Second level

Third level
1. Transitions
are purine-to purine or pyrimidine-to Fourth: level
pyrimidine changes
Fifth level : AG, GA, CT, or TC.
2. Transversions : are purine-to-pyrimidine or
pyrimidine-to-purine changes: AC, AT, GC,
GT, CA, CG, TA or TG
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In-frame mutation maintain reading

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frame (codon is intact)

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Out
frame/frame-shift
mutation
disruptlevel
reading frame
Second
Third level
Fourth
level
Point
mutation:
Single nucleotide change
Fifth level
- deletion
- insertion
- missense
- nonsense (create a stop codon)
- silent (no amino acid alteration)

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Point mutation :

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Missense

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Second level
Silent

Third level

Missense

Fourth level
Fifth level

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Deletion mutation:

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In-frame

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Second level
Third level
Fourth level
Fifth level

Out of frame

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Effects of mutation
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Change in a morphological trait

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Nutritional or biochemical variation
Second level
Change
in behavior
Third level
Fourth
level
Changes
in gene
regulation
Fifth level
Lethality

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Chemical Mutagenesis

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Proflavine, causes addition or deletion of

during
synthesis of new DNA
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strands.

Second level

Nitrous acid, replacing amino groups with

Third level
keto groups. DNA treated with nitrous
Fourth level
acid produces errors during subsequent
Fifth level
replications.

5-bromouracil, resemble the natural

bases that they can be mistakenly

incorporated into DNA at the time of
replication.
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Screening
system
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The Ames test

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to suggest whether a compound is

to suggest whether a compound is

Second
level
mutagenic
or carcinogenic in animals
by determining
whether it is
Third
level
mutagenic
in bacteria.
Fourth level
Sister
chromatid
exchange
Fifth
level
after exposing the cells in vitro to
the test chemical, researcher look at
metaphase for chromosomal defects
of various type.
Blue mouse test
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Radiation
Mutagenesis
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beedit
mutagenic
radiant
Second
reachlevel
DNA directly or nearby
Third level dose: the amount of
Radiation
Fourth level
radiation
absorbed by given amount of
Fifth level
substance
> units : rontgent, rad, rem, gray
Is there a threshold or safe dose?
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Second level
Third level
Fourth level
Fifth level

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Radiation
Effects
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Somatic Effect
- respect to chronic or low-level

ionizing radiation
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- possible induction of cancer

Secondeffect
Germinal
level

- possible
induction
Third
level of point mutation or
chromosomal aberrations
Fourth level
- may cause harm to immediate off spring
Fifth level
or later descendants
- Estimation: 1 rad per generation produces
1 case of genetic disease per 50.000 births in
the children of those exposed

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Third level
Fourth level
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Conclusions

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Mutation is the key processes responsible for

the variability in the genome

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Second level
Mutation has various effects on genome
Third level
function Fourth level
Fifth level

Some cells can modify their repair processes to

induce hypermutation and bacteria may be able to
carry out programmed mutations
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Most mutations can be corrected by DNA repair

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processes
include:text styles
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excision
Secondprocedures
by removing damaged
level
Thirdand
level
nucleotides
Fourth level
mismatch
repair
systems for correcting
Fifth level
replication errors.

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Polymorphism:

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Different nucleotide sequence that occurs in the population

as a whole

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Second level

Deletion

Third level

Insertion Fourth level

Duplication Fifth level
Missense
Silent

Patient (+)
Control (-)

Mutation

Patient (+)
Control (+)

Polymorphism

Most polymorphism occurs in intronic sequence

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Biological
system
hierarchy
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supra individual: bio-socio-cultural

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Ecosystem
Second level
Species
Third level
Supranational
Fourth level
Fifth level
National
Community
Family
Individual organism

environmental health
international health
regional health
public health
community medicine*
family medicine
personal medicine
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Biological system hierarchy

infra
individual:
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Organism
Second level
Organ system
Third level
Organ
Fourth level
Fifth level
Tissue
Cellular
Molecular
Submolecular

Biomedical sciences:
anatomy, physiology,
biochemistry,
histology, cell biology,
genetics,
medical chemistry,
medical physics, etc.
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