MUTATION

The replication and distribution of genetic material is extremely

accurate so that the genetic information is usually passed on from
one generation to the next without alteration.
But, occasionally errors do occur both during replication and
distribution of the genetic material giving rise to sudden heritable
changes in the characters of organisms .
such alterations are called mutations , while individuals showing
these changes are known as mutants.
A mutations may arise due to a change in the base sequence of a
gene. Such mutations are called as gene mutations or point
mutations.
But changes in chromosomal number and structure also produce
heritable changes in phenotype; these are termed as chromosomal
mutations.
MUTAGENS
Class
Physical mutagens
1.Ionizing radiations
-particulate radiations
-non-particulate radiations
2.Non-ionizing radiations
Chemical mutagens
1.Alkylating agents
-base analogues
-acridine dyes
2.Deamination agents
-other chemical mutagens
Mutagen
-Alpha ,beta ,fast neutrons,
thermal neutrons
-X-rays, gamma rays
-UV rays
-mustard gas, nitrogen mustard,
EMS,MMS,EES.
-5-bromouracil,2-amino purine
-acriflavin,proflavin,acridine
orange.
-nitrous acid (HN02)
-hydroxylamine, sodium azide.
EMS-ethylmethane sulphonate,
MMS-methylmethane sulphonate,
EES-ethylene sulphonate.
 POINT MUTATION
A point mutation, or single base substitution, is a type of mutation
that causes the replacement of a single base nucleotide with another
nucleotide of the genetic material, DNA or RNA.
A point mutant is an individual that is affected by a point mutation.
There are also three types of point mutations, namely a missense
mutation , nonsense mutation and silent mutation.
Causes of point mutations
Point mutation is a random SNP (single-nucleotide polymorphism)
mutation in the deoxyribonucleic acid (DNA) that occurs at one point.
DNA replication occurs when one double-stranded DNA molecule
creates two single strands of DNA
A single point mutation can change the whole DNA sequence.
Changing one purine or pyrimidine may change the amino acid that
the nucleotides code for.
 Point mutations may arise from spontaneous mutations that occur
during DNA replication. The rate of mutation may be increased by
mutagens.
Mutagens can be physical, such as radiation from UV rays, X-rays or
extreme heat, or chemical (molecules that misplace base pairs or
disrupt the helical shape of DNA). Mutagens associated with cancers
are often studied to learn about cancer and its prevention.
There are multiple ways for point mutations to occur. First,
ultraviolet(UV) light and higher-frequency light are capable ionizing
electrons and in turn impacting DNA.
Also, one of the cell metabolic byproducts, reactive oxygen molecules
with free radicals, can also be very harmful to DNA. These reactants
can lead to both single-stranded DNA breaks and double-stranded
DNA breaks. Third, bonds in DNA eventually degrade, which creates
another problem to keep the integrity of DNA to a high standard.
There can also be replication errors that lead to substitution,
insertion, or deletion mutations.
CATEGORIZING POINT MUTATIONS
Transition/Transversion categorization
In 1959 Ernst Freese coined the terms "transitions" or
"transversions" to categorize different types of point mutations.
Transitions: replacement of a purine base with another purine or
replacement of a pyrimidine with another pyrimidine
Transversions: replacement of a purine with a pyrimidine or vice
versa.
Transitions (Alpha) and Transversions (Beta).
CENTRAL DOGMA OF MOLECULAR
BIOLOGY
FUNCTIONAL CATEGORIZATION
Nonsense mutations:

Code for a stop, which can truncate the protein. A

nonsense mutation converts an amino acid codon into a
termination codon. This causes the protein to be
shortened because of the stop codon interrupting its
normal code.
 Missense mutations:

Code for a different amino acid. A missense mutation changes a

codon so that a different protein is created, a non-synonymous
change.
 Silent mutations:
Code for the same amino acid. A silent
mutation has no effect on the functioning
of the protein. A single nucleotide can
change, but the new codon specifies the
same amino acid, resulting in an
unmutated protein.
This type of change is called synonymous
change, since the old and new codon code
for the same amino acid. This is possible
because 64 codons specify only 20 amino
acids.
SPECIFIC DISEASES CAUSED BY POINT
MUTATIONS
Cystic fibrosis
A defect in the cystic fibrosis transmembrane conductance regulator (CFTR)
gene causes cystic fibrosis (CF). A protein made by this gene controls the
movement of the water and salt in and out of the body's cells. Genes in
people with CF incorrectly code proteins. This causes thick, sticky mucus
and very salty sweat.
Neurofibromatosis
Neurofibromatosis is caused by point mutations in the Neurofibromin 1or
Neurofibromin 2 gene.
Sickle-cell anemia
Sickle-cell anemia is caused by a point mutation in the -globin chain of
haemoglobin, causing the hydrophilic amino acid glutamic acid to be
replaced with the hydrophobic amino acid valine at the sixth position.
Color blindness
People who are colorblind have mutations in their genes that cause a loss of
either red or green cones
 FRAMESHIFT MUTATION
Inserting or deleting one or more nucleotides
Changes the reading frame like changing a sentence
Proteins built incorrectly
addition of a new letter (base) in the DNA sequence
deletion of a letter (base) in the DNA
both of these shift the DNA
A frameshift mutation is not the same as a single-nucleotide
polymorphism in which a nucleotide is replaced, rather than
inserted or deleted.
 DISEASES ASSOCIATED WITH FRAMESHIFT
MUTAITION
Crohn's Disease
Crohn's Disease has an association with the NOD2 gene. The
mutation is an insertion of a Cytosine at position 3020. This leads to
a premature stop codon, shortening the protein that is supposed to
be transcribed. When the protein is able to form normally, it
responds to bacterial liposaccharides, where the 3020insC mutation
prevents the protein from being responsive.
Cystic Fibrosis
(CF) is a disease based on mutations in the CF transmembrane
conductance regulator (CFTR) gene. There are over 1500 mutations
identified, but not all cause the disease. Most cases of cystic fibrosis
are a result of the F508 mutation, which deletes the entire amino
acid. Two frameshift mutations are of interest in diagnosing CF,
CF1213delT and CF1154-insTC.
They both lead to a small decrease in the function of the lungs and
occur in about 1% of patients tested.
Tay-Sachs Disease
Is a fatal disease affecting the central nervous system. It is most frequently found in
infants and small children.
(SMS)is a complex syndrome involving intellectual disabilities, sleep disturbance,
behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies.
The majority of SMS cases harbor an ~3.5 Mb common deletion that encompasses
the retinoic acid induced-1 (RAI1) gene. Most of the mutations observed (65/78) are
single base substitutions or SNPs, 11 deletions, 1 large and 10 small, and 2
insertions.
Smith-Magenis Syndrome
(SMS)is a complex syndrome involving intellectual disabilities, sleep disturbance,
behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies.
The majority of SMS cases harbor an ~3.5 Mb common deletion that encompasses
the retinoic acid induced-1 (RAI1) gene.
Hypertrophic Cardiomyopathy
Is the most common cause of sudden death in young people, including trained athletes,
and is caused by mutations in genes encoding proteins of the cardiac sarcomere.
Mutations in the Troponin C gene (TNNC1) are a rare genetic cause of hypertrophic
cardiomyopathy. A recent study has indicated that a frameshift mutation (c.363dupG or
p.Gln122AlafsX30) in Troponin C was the cause of hypertrophic cardiomyopathy (and
sudden cardiac death) in a 19-year-old male.
 CHROMOSOMAL ABERRATIONS

conception
s

Spontaneo
Live births us
abortions

Chromoso
Perinatal mal
children
deaths abnormaliti
es