Mutation

- is a change of the nucleotide

sequence of the genome of an
organism, virus, or extra
chromosomal genetic
element.
 Types of Mutation
• Substitution
• Insertion
• Deletion
• Frameshift
 Substitution
A substitution is a mutation
that exchanges one base for
another (i.e., a change in a
single "chemical letter" such as
switching an A to a G).
 Insertion
Insertions are
mutations in which extra
base pairs are inserted
into a new place in the
DNA.
 Inversion
a DNA sequence of
nucleotides is reversed.
Inversions can occur among a
few bases within a gene or
among longer DNA sequences
that contain several genes.
 Deletion
Deletions are
mutations in which a
section of DNA is lost, or
deleted.
 Frameshift
Since protein-coding DNA is
divided into codons three bases
long, insertions and deletions
can alter a gene so that its
message is no longer correctly
parsed.
Chromosomal
Variation in
Number
 Aneuploidy
- the abnormal condition
were one or more
chromosomes of a normal set of
chromosomes are missing or
present in more than their usual
number of copies.
 Nullisomy
- the loss of both pairs of
homologous chromosomes
- nullisomics
- 2N-2
 Monosomy
-the loss of a single
chromosome
-monosomics
-2N-1
 Trisomy
- the gain of an extra copy of
a chromosome;
- trisomics
- 2N+1
 Tetrasomic
- the gain of an extra pair of
homologous chromosomes
- Tetrasomics
- 2N+2
 Gene Mutation
is a permanent change in the
DNA sequence that makes up a
gene. Mutations range in size from
a single DNA building block (DNA
base) to a large segment of a
chromosome.
 Inherited
• hereditary mutations or germline
mutations
• This type of mutation is present
throughout a person’s life in
virtually every cell in the body.
 Acquired
• or somatic mutations
• occur in the DNA of individual cells
at some time during a person’s life.
• caused by environmental factors
• cannot be passed on to the next
generation.
How Causes
Mutations
To Occur?
 Natural Cause
• DNA fails to copy accurately
–when a cell divides, it makes a
copy of its DNA and sometimes
the copy is not quite perfect.
External Influences/Mutagens

In genetics, a mutagen is a
physical or chemical agent that
changes the genetic material,
usually DNA, of an organism and
thus increases the frequency of
mutations above the natural
background level.
 Effects of mutagens
• can affect the transcription and
replication of the DNA,
• can lead to cell death.
• produces mutations that can result in
aberrant, impaired or loss of function for
a particular gene,
• accumulation of mutations may lead to
cancer.
• (chromosomal
instability)chromosomal breakages
and rearrangement of the
chromosomes such as translocation,
deletion, and inversion. (clastogens)
• Some mutagens can cause
aneuploidy and change the number
of chromosomes in the cell.
Types of
Mutagens
 Physical mutagens
• Ionizing radiations such as X-rays,
gamma rays and alpha particles
–may cause DNA breakage and other
damages. The most common sources
include cobalt-60 and cesium-137.
• Radioactive decay
• Ultraviolet radiations with
wavelength above 260 nm
– are absorbed strongly by bases, producing
pyrimidine dimers, which can cause error in
replication if left uncorrected.
• DNA reactive chemicals
– A large number of chemicals may interact
directly with DNA. However, many are not
necessarily mutagenic by themselves, but
through metabolic processes in cells they
produce mutagenic compounds.
• Reactive oxygen species (ROS)
– These ROS may result in the production of many
base adducts, as well as DNA strand breaks and
crosslinks.
• Deaminating agents
– for example nitrous acid which can cause
transition mutations by converting cytosine to
uracil.
• Aromatic amines and amides
– have been associated with carcinogenesis, may
cause cancer of the bladder, liver, ear, intestine,
thyroid and breast
 Biological Agents
• Virus
– Virus DNA may be inserted into the genome and
disrupts genetic function. Infectious agents have
been suggested to cause cancer.
• Bacteria
– some bacteria such as Helicobacter pylori cause
inflammation during which oxidative species are
produced, causing DNA damage and reducing
efficiency of DNA repair systems, thereby
increasing mutation.
Protection Against
Mutagens
• Fruits and vegetables that are
rich in antioxidants
– Antioxidants are an important group of
anticarcinogenic compounds that may help
remove ROS or potentially harmful
chemicals.
• An effective precautionary measure
an individual can undertake to
protect themselves is by limiting
exposure to mutagens such as UV
radiations and tobacco smoke.
Mutation in
Humans
 Down Syndrome
• also known as trisomy 21, is a genetic disorder
caused by the presence of all or part of a third
copy of chromosome 21.
• It is typically associated with physical growth
delays, characteristic facial features and mild to
moderate intellectual disability.
• The average IQ of a young adult with Down
syndrome is 50, equivalent to the mental age of
an 8 or 9 year old child, but this varies widely.
 Edward’s syndrome
• (also known as Trisomy 18 [T18]) is a
chromosomal disorder caused by the
presence of all or part of an extra 18th
chromosome.
• This genetic condition almost always results
from nondisjunction during meiosis.
• named after John Hilton Edwards, who first
described the syndrome in 1960.
• It is the second most common
autosomal trisomy, after Down
syndrome, that carries to term.

• Characteristics: kidney malformations,

structural heart defects at birth,
intestines protruding outside the body
(omphalocele), intellectual disability,
developmental delays, growth deficiency,
feeding difficulties, breathing difficulties,
and arthrogryposis.
 Patau syndrome
• is a syndrome caused by a chromosomal
abnormality, in which some or all of the cells of
the body contain extra genetic material from
chromosome 13.
• The extra genetic material from chromosome 13
disrupts the normal course of development,
causing multiple and complex organ defects.
 Monosomy 7
• is typically characterized by early-
childhood onset of evidence of bone
marrow insufficiency/failure
associated with increased risk for
myelodysplastic syndrome (MDS) or
acute myelogenous leukemia (AML).
• Bone marrow failure/MDS/AML follows
within a few months to years of
identification of a monosomy 7 cell line
in peripheral blood. Nearly all individuals
reported with familial mosaic monosomy
7 have died of their disease.
 Tetrasomy 18p
• is a genetic condition that is caused by the
presence of an isochromosome, composed of
two copies of the short arm of chromosome 18.
It is characterized by multiple medical and
developmental concerns.
• cryptorchidism among males
• feeding difficulties, respiratory difficulty and
jaundice are also relatively frequent.
Pallister–Killian syndrome
• Pallister–Killian syndrome (also
tetrasomy 12p mosaicism or Pallister
mosaic aneuploidy syndrome) is an
extremely rare genetic disorder occurring
in humans.
• Pallister-Killian occurs due to the
presence of the anomalous extra
isochromosome 12p, the short arm of
the twelfth chromosome.
• Characteristics include varying degrees of
developmental disability, epilepsy, hypotonia,
and both hypopigmentation and
hyperpigmentation.
• Patients also exhibit a distinctive facial
structure, characterized by high foreheads,
sparse hair on the temple, a wide space
between the eyes, epicanthal folds, and a flat
nose.
• Vision and hearing impairments may occur.
Patients may also exhibit congenital heart
defects, gastroesophageal reflux, cataracts,
and supernumerary nipples.
• Diaphragm problems seen in newborns can
lead to death shortly after birth.

• As patients pass into adolescence, the

syndrome is characterized by a coarse and flat
face, macroglossia prognathia, inverted lower
lip, and psychomotor retardation with
muscular hypertonia and contractures.