Gene – Expression –

Mutation - polymorphism

1
 Telomere

1p32.2
Short arm
(p)

Centromere

Long arm
(q)

Telomere
2
Human
Chromosome:

- 22 pair
autosomal
- 1 pair sex

3
Basic genetic principles

22 pasang autosomal kromosom

1 pasang sex kromosome

Laki-laki XY, wanita XX

Total: 46 kromosom

4
 X-linked inheritance:
XY XX

Female carrier
XX XY XX Male patient

XY XY XX XX XY

XX XY XY XX XY XY

5
Factors which can influence the phenotype

6
 How are genes expressed ?

DNA
Transcription
Cap Pre-mRNA
Poly(A)

Splicing
Lariat intron mRNA
Cap Poly(A)

Degradation
Nucleus mRNA transport

Translation

Cytoplasm Ribosome PROTEIN

7
 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

8
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
9
 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.

10
 The cause of mutations

1. Spontaneous error in replication that

evade proofreading function of the DNA
polymerases that synthesize new
polynucleotides
 mismatches

11
1. Error in replication

12
 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.

13
2. Effect of mutagen

14
Mutation :

In-frame mutation  maintain reading frame

(codon is intact)

Out of frame/frameshift mutation  disrupt

reading frame
1. Point mutation
2. Deletion
3. Insertion
4. Duplication

15
16
 Point mutation  common
(single site mutation) : replace one
nucleotide with another
Divided into two catagories:

1. Transitions : are purine-to purine or pyrimidine-to-

pyrimidine changes : AG, GA, CT, or TC.

2. 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

17
Point mutation:
Single nucleotide change 
- deletion
- insertion
- missense
- nonsense (create a stop codon)
- silent (no amino acid alteration)

18
 Point mutation :

Missense

Silent Missense

19
Deletion mutation:

In-frame

Out of frame

20
 Polymorphism:
 Different nucleotide sequence that occurs in
the population as a whole

Deletion Patient (+) Mutation

Insertion Control (-)

Duplication
Missense
Patient (+) Polymorphism
Silent Control (+)

Most polymorphism occurs in intronic sequence

21