MUTASI

Dr. Upik A. Miskad, PhD

Unhas Research Center
DNA
 All genetic variation originates from the process
known as MUTATION -------- A change in DNA
sequence (<1%)

Somatic cell mutation

Mutations

Germline cell mutation

(Transmitted from one generation to
the next)
 Mutations Cause :
DNA sequence of gene among
individual may be differ
The differing sequences ---- alleles

Individual who has same alleles on both member of

chromosome pair ---- homozygote

Individual who has differ alleles on both member of

chromosome pair ---- heterozygote

Polymorphisms
Alleles frequencies are >1% in a population
 Alteration of the number or structure of
chromosome in a cell, microscopically observed
Mutations

Mutations affect single gene,

they are not microscopically observed.

- Take place in coding region

- Take place in regulatory sequences
 MUTATION
• Mutasi adalah perubahan yang terjadi pada rangkain DNA
yang bisa menyebabkan kesalahan genetik.
• Mutasi dapat menyebabkan perubahan protein yang dikode
oleh gen tersebut atau tidak dikodenya pembentukan
protein.
 Genetic Code
he genetic code is read in groups of three nucleotide,
……………called codon
ach group representing one amino acid
 MUTATION
• Mutation refers to the change in a DNA
sequence, which may involve only a few
bases or the large-scale chromosome
abnormality. 

• This section covers the small-scale

mutations
– SUBSTITUTION
– DELETION
– INSERTION
 SUBTITUTION
• In the substitution mutation, one or more
nucleotides are substituted by the same
number of different nucleotides.
• In most cases, only one nucleotide is changed.

• Based on the change in the nucleotide type,

the substitution mutation may be divided into
transition and transversion mutations. 

• Based on the consequence of mutation, the

substitution mutation may be grouped into
silent, missense and nonsense mutations.
 SUBTITUTION
  The substitution mutation. 
(a) Illustration of transition (blue)
and transversion (red) mutations. 

• In the transition mutation, a

pyrimidine (C or T) is substituted
by another pyrimidine, or a purine
(A or G) is substituted by another
purine. 
• The transversion mutation
involves the change from a
pyrimidine to a purine, or vice
versa.
SUBTITUTION
(b) Examples of silent, missense and
nonsense mutations. 

• The silent mutation does not produce

any change in the amino acid
sequence

• The missense mutation results in a

different amino acid, and

• The nonsense mutation generates a

stop signal.
 INSERTION
• In the insertion mutation, one or
more nucleotides are inserted
into a sequence.
• If the number of inserted bases is
not a multiple of 3, it will cause
frameshift, resulting in serious
consequences.
•
 INSERTION
• As shown in the following table, non-frameshift
insertions may also cause diseases.
 DELETION
The deletion mutation involves
elimination of one or more
nucleotides from a DNA
sequence. 
It may cause frameshift, producing a
non-functional protein
 DELETION

Real examples of deletion mutations which cause diseases.    (a) Deletion of "T" from
the sequence "TTTTT" in the CFTR gene.  
(b) Deletion of "AT" from the sequence "ATAT" in the CFTR gene.  
(c) Deletion of "TTG" from the sequence "TTGTTG" in the FIX gene.  
(d) Deletion of "ATAG" from the sequence "ATAGATAG" in the APC gene.
Note that deletion and insertion mutations often occur in the repetitive sequence.  As
explained in the next section, they are usually caused by  "replication slippage".
Deletion and insertion (one or more base pair)
Frameshift mutation,
(can alter all of the downstream codon)
 REPLICATION ERROR
• Replication errors are the main source of mutations. 
• It has been estimated that uncorrected replication errors
occur with a frequency of 10-9 - 10-11 for each nucleotide
added by DNA polymerases. 
• Since a cell division requires synthesis of 6 X 109
nucleotides, the mutation rate is about one per cell
division.  
• A commonly observed replication error is the replication
slippage, which occurs at the repetitive sequences when
the new strand mispairs with the template strand. 
• The microsatellite polymorphism is mainly caused by the
replication slippage. 
• If the mutation occurs in a coding region, it could produce
abnormal proteins, leading to diseases.  The Huntington's
disease is a well known example
Mutation by Replication Errors

• The mutation caused by

replication slippage.  In
this figure, mispairing
involves only one
repeat.  In fact, the
slippage could cause
several repeats to
become unpaired. 
• (a) Normal replication. 
• (b) Backward slippage,
resulting in the insertion
mutation. 
• (c) Forward slippage,
resulting in the deletion
mutation. 
Induced Mutations

Agents causing mutations

Attributed to known environmental causes ……

spontaneous mutations
(naturally arise during DNA replication)

Agents causing mutations are known as mutagen

1. Radiation
………… Ionizing radiation

Eject electron from atom

Forming electrically charged ions Change DNA bases
Break the bonds of ds-DNA

……..... Non ionizing radiation (UV radiation)

Formation of covalent bonds between

adjacent pyrimidine bases
2. Chemical

Base analog …… can subtitute the the true DNA

during replication

Examples :

5-bromouracil
Acridine dyes
Alkylating agent
Nitrogen mustard
 Correcting replication error
(mismatches)
DNA Repair Repairing ds-DNA break
Exciting damage nucletides

Large numbers of mutagens can cause mutations !!!!!!!

Several dozen enzymes are involved in the repair of

DNA damaged.

Defect in the enzymes of DNA Many type of

repair diseases
 DNA REPAIR
• There are three major DNA repairing
mechanisms:

• base excision,
• nucleotide excision and
• mismatch repair. 
 DNA REPAIR
 
• Proteins involved in the DNA repairing of
E. coli.
BASE EXCISION
• DNA's bases may be
modified by deamination or
alkylation. 
• The position of the
modified (damaged) base
is called the "abasic site"
or "AP site". 
• In E.coli, the DNA
glycosylase can recognize
the AP site and remove its
base. 
• Then, the AP endonuclease
removes the AP site and
neighboring nucleotides. 
• The gap is filled by DNA
polymerase I and DNA
ligase. 
 Nucleotide excision

• In E. coli, proteins
UvrA, UvrB, and UvrC
are involved in
removing the
damaged
nucleotides.
• The gap is then filled
by DNA polymerase I
and DNA ligase. 
 DNA RECOMBINATION
• DNA recombination refers to the process that a
DNA segment moves from one DNA molecule to
another DNA molecule.  The following three types
are most commonly observed.

• Homologous recombination
• Site-specific recombination
• Transpositional recombination

• The homologous recombination often occurs

during meiosis.  Other types of recombination are
not specifically related to cell division.
• Comparison between gene conversion and DNA crossover.
• (a) Two DNA molecules.
• (b) Gene conversion - the red DNA donates part of its
genetic information (e-e' region) to the blue DNA. 
• (c) DNA crossover - the two DNAs exchange part of their
genetic information (f-f' and F-F').
•Thank you and Good Luck