1. M. Mansyur Romi Dept. of Anatomy, Embryology & Anthropology
GENE MUTATION
M. Mansyur Romi
Dept. of Anatomy, Embryology & Anthropology

2. Mutation:
any heritable change in the nucleotide sequence of genomic DNA caused by a replication error or by a mutagen.
Mutagen  a chemical or physical agent that can cause a mutation in a DNA molecule

4. Type of mutations Where occur: * Gametic or germinal mutation
* Somatic mutation
How occur:
* Spontaneous mutation
* Induced mutation
* Directed (adaptive) mutation

5. Germinal Mutation Somatic Mutation
Occurs in a cell that is destined to become an egg or sperm
Is transmitted to future generations
Somatic Mutation
Occurs in a body cell ( liver, bone etc) not ancestral to gametes.
Can affect to phenotype of its carrier

6. Spontaneous Mutation
Arise as a natural errors in replication that evade proofreading function of the DNA polymerases that synthesize new polynucleotide  mismatches
Result from random thermal motions of atoms and molecules in and near the DNA
Small portion and due to foreign chemicals or radiation that get inside cells and near the DNA

7. 1. Error in replication

8. Mutation rate (  )
The frequency of mutation expressed as the number of mutation per locus per gamete per generation
E. coli ~ 1/108 : 1 error in every 108 replication
Humans ~ 1/106 – 1/105 : due to a higher complexity of human replication

9. Induced Mutation
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

10. 2. Effect of mutagen

11. Directed (Adaptive) Mutation
Arises not as a result of blind variation on the genetical level and consequent selection, but by some sort of purposeful behavior of the cell as a whole
The cell is 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

12. Size of Material mechanism: Point mutation
single nucleotide change not
visible under a microscope
Broad mutation
microscopically visible aberration
mechanism:
deletion
insertion
substitution (transversion, transition) etc

14. Point mutation  common
(single site mutation) : replace one nucleotide with another
Divided into two categories:
Transitions : are purine-to purine or pyrimidine-to-pyrimidine changes : AG, GA, CT, or TC.
Transversions : are purine-to-pyrimidine or pyrimidine-to-purine changes: AC, AT, GC, GT, CA, CG, TA or TG

15. In-frame mutation  maintain reading frame (codon is intact)
Out of frame/frame-shift mutation  disrupt reading frame
Point mutation: Single nucleotide change 
- deletion
- insertion
- missense
- nonsense (create a stop codon)
- silent (no amino acid alteration)

16. Point mutation :
Missense
Missense
Silent

17. Deletion mutation:
In-frame
Out of frame

18. Effects of mutation Change in a morphological trait
Nutritional or biochemical variation
Change in behavior
Changes in gene regulation
Lethality

19. Chemical Mutagenesis
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.

20. 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.
Blue mouse test

21. 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”?

23. Radiation Effects Somatic Effect Germinal effect
- respect to chronic or low-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 births in
the children of those exposed

25. Conclusions
Mutation is the key processes responsible for the variability in the genome
Mutation has various effects on genome function
Some cells can modify their repair processes to induce hypermutation and bacteria may be able to carry out programmed mutations

26. Most mutations can be corrected by DNA repair processes which include:
excision procedures by removing damaged nucleotides and
mismatch repair systems for correcting replication errors.

27. Polymorphism: Most polymorphism occurs in intronic sequence
 Different nucleotide sequence that occurs in the population as a whole
Deletion
Insertion
Duplication
Missense
Silent
Patient (+)
Control (-)
Control (+)
Mutation
Polymorphism
Most polymorphism occurs in intronic sequence

28. Biological system hierarchy supra individual: bio-socio-cultural
Ecosystem  environmental health
Species  international health
Supranational  regional health
National  public health
Community  community medicine*
Family  family medicine
Individual organism  personal medicine

29. Biological system hierarchy infra individual: bio-physico-chemistry
Organism Biomedical sciences:
Organ system anatomy, physiology,
Organ biochemistry,
Tissue histology, cell biology,
Cellular genetics,
Molecular medical chemistry,
Submolecular medical physics, etc.