Mutations are heritable changes in an organism's genetic material. They arise from errors in DNA replication or distribution and can cause sudden changes in characteristics. There are two main types of mutations - gene mutations, which alter the sequence of a single gene, and chromosomal mutations, which involve changes in chromosome number or structure. Point mutations specifically change a single DNA nucleotide, and can be further classified as transitions, transversions, nonsense, missense, or silent mutations depending on their effects. Frameshift mutations insert or delete DNA nucleotides, altering the reading frame and resulting in abnormal proteins. Many diseases like cystic fibrosis, sickle cell anemia, and cancer are caused by specific point or frameshift mutations.

2. 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.

3. MUTAGENS
Class Mutagen
Physical mutagens
1.Ionizing radiations
-particulate radiations
-non-particulate radiations
2.Non-ionizing radiations
-Alpha ,beta ,fast neutrons, thermal
neutrons
-X-rays, gamma rays
-UV rays
Chemical mutagens
1.Alkylating agents
-base analogues
-acridine dyes
2.Deamination agents
-other chemical mutagens
-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.

4. 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.

5.  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.

6. 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).

7. CENTRAL DOGMA OF MOLECULAR BIOLOGY

8. 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.

9. • 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.

10. • 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.

11. 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 β-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

12. 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.

14. 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.

15. 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

16. CHROMOSOMAL ABERRATIONS
conceptions
Live births
children
Perinatal
deaths
Spontaneous
abortions
Chromosomal
abnormalities