Mutations

Mutation
These are changes to the base pair sequence of
genetic material (either DNA or RNA).
It can be caused by copying errors in the
genetic material during cell division and by
exposure to ultraviolet or ionizing radiation,
chemical mutagens, viruses, or can occur
deliberately under cellular control during
processes such as meiosis or hypermutation.

 They may be cytologically visible in

the nucleus as chromosome
changes or cytologically invisible
gene or point mutations
Both kinds have observable
developmental effect on the
phenotype of an organism

Changes in chromosome number

Changes in gene
Caused by nature
Caused by artificial method

Chromosome variation in number

1. Euploidy- refers to the changes
involving the whole genome or the
entire set of chromosome
Monoploid (1)- ABC
Diploid (2) AABBCC
Polyploid- tetraploid, pentaploid,
hexaploid,heptaploid, octaploid

Identify the euploidy type:

CCCCCCCC

~OCTAPLOID

Identify the euploidy type:

LLLLLLLLLLMMMMMMMMMMNNNNNNNNNN

~DECAPLOID

Polyploid
Refers to any organism in
which the number of
complete chromosomes sets
exceeds that of a diploid.

Reasons for polyploidy

1. Fertilization of an egg by more than
one sperm leading to a zygote
nucleus with 3 or more sets of
chromosomes.
2. Failure of mitosis that multiplies the
number of somatic chromosomes in
a sex organ , thereby increasing the
number of gametic chromosomes.
3. Failure in meiosis that produces a
diploid gamete instead of a haploid.

Aneuploidy
Occurs when one or more
chromosomes of a normal set
(genome) are lacking or are present
in excess.
The nuclei will contain chromosomes
whose numbers are not multiples of
the genome.
Characterized by incomplete

Types:

Disomic (2N)- AABBCC

Monosomic- (2N-1)- AABBC
Nullisomic- (2N-2) AABB_ _
Polysomic extra chromosomes
Trisomic- AABBCCC
Double trisomic, tetrasomic,pentasomic,.

Identify the type of aneuploidy

1. AABBCCCCC
2. AAAAAABBCC
3. AABBBBBBBCC
4. AABBBCCC

Trisomy in humans:
The occurrence of aneuploidy for
autosomal chromosomes in
humans is often lethal since a
change an autosomal dosage
lacks the inactivation mechanism
that seems to operate for
additional chromosomes.
Example- Down syndrome,
trisomy 21

Down syndrome
Triplo21 trisomic for
autosome 21
Translocation- extra 21
chromosome to another
chromosome 14,15 or 21

Patau syndrome

also known as trisomy 13, is a

chromosomal abnormality, a syndrome in
which a patient has an additional
chromosome 13 due to a non-disjunction
of chromosomes during meiosis. Some are
caused by Robertsonian translocations.
The extra chromosome 13 disrupts the
normal course of development, causing
the characteristic features of Patau
syndrome. Like all non-disjunction
diseases (Down syndrome, Edwards
syndrome, etc.), the risk of disease in the
offspring increases with maternal age at
pregnancy, with about 31 years being the
average.
Patau syndrome affects approximately 1 in

Edward syndrome

is a genetic disorder caused by the presence of

all or part of an extra 18th chromosome.
It is named after John H. Edwards, who first
described the syndrome in 1960.
It is the most common autosomal trisomy,
after Down Syndrome, that carries to term.
Trisomy 18 is caused by the presence of three
as opposed to two copies of chromosome
18 in a fetus or infant's cells.
The incidence of the syndrome is estimated as
one in 3,000 pregnancies and approximately
one in 6,000 live births.
The incidence increases as the mother's age
increases. The syndrome has a very low rate of
survival, resulting from heart abnormalities,
kidney malformations, and other internal organ

Changes in chromosome
structure
Chromosome usually remains the
same, but their genetic material
becomes altered through the loss,
gain or rearrangement of particular
sections.

Chromosomal rearrangements
1. Deficiencies or Deletions
- loss in chromosomal material
- Cri du chat syndrome
(Chromo#5)
- Philadelphia 22
Kinds:
a. Interstitial deficiency
b. Terminal

2. Duplication or repeats
- is the presence of a section of a
chromosome in excess of the
normal amount.
- the repeated section of
chromosomal material may be
present in one pair of homologous
chromosomes may have been
transposed to a nonhomologous on
occasion; may even exist
independently with its own
centromere.

Types:
a. Tandem
b. reverse
tandem
c. displaced
d. transposition
e. extra
chromosome

a b c d e de

a b c d e ed
a de b c d e
k l m n o 0 p q r de s t
de

3. Inversion
- It is the rotation of a chromosome segment to
a full 180 degrees
- It develops most likely when breaks occur at a
place where a chromosome forms a tight loop
during synapsis.
Types:
a. Pericentric includes the centromere
b. Paracentric does not include the centromere

4. Translocation
- transfer of a section of one chromosome
to a non-homologous chromosome
Types:
a. Simple translocation involves a single
break
b. Shifts involves 3 breaks
c. reciprocal occurs when single breaks in
2 non-homologous chromosome produce
an exchange of chromosome section

Gene Mutations

Any kind of mutation is basically a

change in the DNA which leads to a
corresponding change in
phenotype.
Point mutations

 Most common is the transition that exchanges a

purine for a purine (A G) or a pyrimidine for a
pyrimidine, (C T). A transition can be caused by
nitrous acid, base mis-pairing, or mutagenic base
analogs such as 5-bromo-2-deoxyuridine (BrdU).
Less common is a transversion, which
exchanges a purine for a pyrimidine or a
pyrimidine for a purine (C/T A/G).
A point mutation can be reversed by another
point mutation, in which the nucleotide is
changed back to its original state (true reversion)
or by second-site reversion (a complementary
mutation elsewhere that results in regained gene
functionality). These changes are classified as
transitions or transversions. An example of a
transversion is adenine (A) being converted into a

 There are also many other examples

that can be found. Point mutations that
occur within the protein coding region of
a gene may be classified into three
kinds, depending upon what the
erroneous codon codes for:
Silent mutations: which code for the
same amino acid.
Missense mutations: which code for a
different amino acid.
Nonsense mutations: which code for a
stop and can truncate the protein.

Harmful and beneficial

mutations

Harmful mutations
Changes in DNA caused by mutation can cause errors
in protein sequence, creating partially or completely
non-functional proteins. To function correctly, each cell
depends on thousands of proteins to function in the
right places at the right times. When a mutation alters
a protein that plays a critical role in the body, a medical
condition can result. A condition caused by mutations
in one or more genes is called a genetic disorder.
However, only a small percentage of mutations cause
genetic disorders; most have no impact on health. For
example, some mutations alter a gene's DNA base
sequence but dont change the function of the protein
made by the gene.
If a mutation is present in a germ cell, it can give rise to
offspring that carries the mutation in all of its cells. This
is the case in hereditary diseases.

 On the other hand, a mutation can occur

in a somatic cell of an organism. Such
mutations will be present in all
descendants of this cell, and certain
mutations can cause the cell to become
malignant.
Often, gene mutations that could cause a
genetic disorder are repaired by the DNA
repair system of the cell. Each cell has a
number of pathways through which
enzymes recognize and repair mistakes in
DNA. Because DNA can be damaged or
mutated in many ways, the process of
DNA repair is an important way in which
the body protects itself from disease

Beneficial mutations

A very small percentage of all mutations actually have a

positive effect.

These mutations lead to new versions of proteins that

help an organism and its future generations better adapt
to changes in their environment.

For example, a specific 32 base pair deletion in human

CCR5 confers HIV resistance to homozygotes and delays
AIDS onset in heterozygotes.

The CCR5 mutation is more common in those of European

descent. One theory for the etiology of the relatively high
frequency of CCR5-32 in the European population is that
it conferred resistance to the bubonic plague in mid-14th
century Europe. People who had this mutation were able
to survive infection thus its frequency in the population
increased.

 A mutant is an individual, organism, or new

genetic character arising or resulting from
an instance of mutation, which is a sudden
structural change within the DNA of a gene
or chromosome of an organism resulting in
the creation of a new character or trait not
found in the wildtype.
In an organism or individual, the new
character or trait may or may not be trivial,
may occasionally be beneficial, but will
usually result in either a genetic disorder or
have no phenotypic effect whatsoever. The
natural occurrence of genetic mutations is
integral to the process of evolution. A more
general term for mutant is sport, which
includes individuals who vary from type due

 In multicellular organisms,
mutations can be subdivided into
germ line mutations, which can
be passed on to descendants, and
somatic mutations. The somatic
mutations cannot be transmitted to
descendants in animals

 Mutations create variations in the gene pool, and the

less favorable (or deleterious) mutations are removed
from the gene pool by natural selection, while more
favorable (beneficial or advantageous) ones tend to
accumulate, resulting in evolutionary change.
For example, a butterfly may develop offspring with a
new mutation caused s by ultraviolet light from the sun.
In most cases, this mutation is not good, since
obviously there was no 'purpose' for such change at the
molecular level. However, sometimes a mutation may
change the butterfly's color, making it harder for
predators to see it; this is an advantage and the
chances of this butterfly surviving and producing its
own offspring are a little better, and over time the
number of butterflies with this mutation may form a
large percentage of the species.
Neutral mutations are defined as mutations whose
effects do not influence the fitness of either the species
or the individuals who make up the species. The
overwhelming majority of mutations have no significant
effect, since DNA repair is able to mend most changes

Causes of mutation
Two classes of mutations are spontaneous
mutations (molecular decay) and induced
mutations caused by mutagens.
Spontaneous mutations on the molecular level
include:

Tautomerism - A base is changed by the repositioning of a

hydrogen atom.
Depurination - Loss of a purine base (A or G).
Deamination - Changes a normal base to an atypical base;
C U, (which can be corrected by DNA repair
mechanisms), or spontaneous deamination of 5methycytosine (irreparable), or A HX (hypoxanthine).
Transition - A purine changes to another purine, or a
pyrimidine to a pyrimidine.
Transversion - A purine becomes a pyrimidine, or vice
versa.

Induced mutations on the molecular level can be

caused by:

Chemicals
Nitrosoguanidine (NTG)
Hydroxylamine NH3OH
Base analogs (e.g. BrdU)
Simple chemicals (e.g. acids)
Alkylating agents (e.g. N-ethyl-N-nitrosourea (ENU)) These
agents can mutate both replicating and non-replicating
DNA. In contrast, a base analog can only mutate the DNA
when the analog is incorporated in replicating the DNA.
Each of these classes of chemical mutagens has certain
effects that then lead to transitions, transversions, or
deletions.
Methylating agents (e.g. ethyl methanesulfonate(EMS))
Polycyclic hydrocarbons (e.g. benzopyrens found in
internal combustion engine exhaust)
DNA intercalating agents (e.g. ethidium bromide)
DNA crosslinker (e.g. platinum)
Oxidative damage caused by oxygen (O)] radicals

 Radiation

Ultraviolet radiation (nonionizing radiation) - excites

electrons to a higher energy level. DNA absorbs one form,
ultraviolet light. Two nucleotide bases in DNA - cytosine and
thymine-are most vulnerable to excitation that can change
base-pairing properties. UV light can induce adjacent thymine
bases in a DNA strand to pair with each other, as a bulky
dimer.
Ionizing radiation

DNA has so-called hotspots, where mutations occur up to 100

times more frequently than the normal mutation rate A hotspot
can be at an unusual base, e.g., 5-methylcytosine.

Mutation rates also vary across species. Evolutionary biologists

have theorized that higher mutation rates are beneficial in some
situations, because they allow organisms to evolve and therefore
adapt more quickly to their environments. For example, repeated
exposure of bacteria to antibiotics, and selection of resistant
mutants, can result in the selection of bacteria that have a much
higher mutation rate than the original population.