1. Gene – Expression – Mutation - polymorphism

2. Telomere
1p32.2
Short arm
(p)
Centromere
Long arm
(q)
Telomere

3. Human Chromosome:
22 pair autosomal
1 pair sex

4. Basic genetic principles
22 pasang autosomal kromosom
1 pasang sex kromosome
Laki-laki XY, wanita XX
Total: 46 kromosom

5. X-linked inheritance:XY XX
Female carrier
Male patient XX XY XX XY XY XX XX XY XX XY XY XX XY XY

6. Factors which can influence the phenotype

7. How are genes expressed ?
DNA
Transcription
Pre-mRNA
Cap
Poly(A)
Splicing
Lariat intron
mRNA
Cap
Poly(A)
Degradation
Nucleus
mRNA transport
Translation
Cytoplasm
Ribosome
PROTEIN

8. MUTATION
Mutation is a change in the nucleotide sequence of genome, caused by a replication error or by a mutagen.
Mutagen  a chemical or physical agent that can cause a mutation in a DNA molecule

9. Consepts
Mutation is the key processes responsible for genome evolution
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

10. Consepts ……
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.

11. The cause of mutations
Spontaneous error in replication that evade proofreading function of the DNA polymerases that synthesize new polynucleotides
 mismatches

12. 1. Error in replication

13. The cause of mutations
2. A mutagen that has reacted with the parent DNA, causing a structural change that affects the base-pairing capability of the altered nucleotide.

14. 2. Effect of mutagen

15. Mutation :
In-frame mutation  maintain reading frame (codon is intact)
Out of frame/frameshift mutation  disrupt reading frame
Point mutation
Deletion
Insertion
Duplication

17. Point mutation  common
(single site mutation) : replace one nucleotide with another
Divided into two catagories:
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

18. Point mutation:
Single nucleotide change 
- deletion
- insertion
- missense
- nonsense (create a stop codon)
- silent (no amino acid alteration)

19. Point mutation :
Missense
Missense
Silent

20. Deletion mutation:
In-frame
Out of frame

21. Polymorphism:
 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