Mutation

Oleh: E. Suryadi
Fakultas Kedokteran UGM
Mutation:
any permanent heritable change in
sequence of genomic DNA

Mutation rate ( )
expressed as the n of mutation per locus
per gamete per generation

Where occur:
* Germinal mutation
* Somatic mutation

How occur:
* Spontaneous mutation
* Induced mutation

Size of Material
Point mutation
* not visible under a microscope
* mechanism: - base substitution
- frame shift

Broad mutation
* microscopically visible aberration
* mechanism: deletion, insertion, etc

Occurs in a cell that is
destined to become an egg or
sperm
Transmitted to future
generations

Occurs in a body cell ( liver, bone
etc) not ancestral to gametes.

Can affect to phenotype of its
carrier

Result from random thermal
motions of atoms and molecules in
and near DNA

Small portion and due to foreign
chemicals or radiation that get
inside cells and near DNA

Following exposure to an agent, a
mutagen, known to produce mutation above
the rate at which they occurs spontaneously.

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

Proflavine, causes addition or deletion of
single bases during synthesis of new DNA
strands.
Nitrous acid, replacing amino groups with
keto groups. DNA treated with nitrous acid
produces errors during subsequent
replications.
5-bromouracil, resemble the natural bases
that they can be mistakenly incorporated into
DNA at the time of replication.

Screening system
The Ames test
to suggest whether a compound is
mutagenic or carcinogenic in animals by
determining whether it is mutagenic in
bacteria.

Sister Chromatid exchange
after exposing the cells in vitro to the test
chemical, researcher look at metaphase for
chromosomal defects of various type.

Radiation Mutagenesis
To be mutagenic radiant energy must
reach DNA directly or nearby
Radiation dose: the amount of radiation
absorbed by given amount of substance
> units : rontgent, rad, rem, gray
Is there a threshold or safe dose

Somatic Effect
- respect to chronic or lour-level
ionizing radiation
- possible induction of cancer
Germinal Effect
Possible induction of point mutation or
chromosomal aberrations
- May cause harm to immediate off spring
or later descendants
- Estimation: 1 rad per generation produces
1 case of genetic disease per 50.000 births in
the
- Children of those exposed