Assignment

GENETICS
Topic:
Gene mutation.

Submitted to:

Miss bushra.

Submitted by:

Kainat Shahid -4155111

Mahrose Nawaz -4155126
Fatima Ashraf -415512
Nousheen Fatima -415511
Farwa Altaf -415513

Department Of Biotechnology
Lahore College for Women University

GENE MUTATION
KAINAT SHAHID-4155111

Gene mutation:

Gene mutation is abrupt inheritable qualitative or quantitative

change in the genetic material of an organism.
Since in most organisms genes are segments of DNA molecule, so a
mutation can be regarded as a change in the DNA sequence which is
reflected in the change of sequence of corresponding RNA or protein
molecules. Such a change may involve only one base/base pair or
more than one base pair of DNA.
Mutations occur in a random manner, i.e., they are not directed
according to the requirements of the organism. Most mutations
occur spontaneously by the environmental effect ,however, they can
be induced in the laboratory either by radiations, physical factors or
chemicals (called mutagens). A unicellular organism is more
subjected to environmental on-slaughts since it is at the same time a
somatic or germ cell.
In multi cellular organisms the germ cells are distinct cells, and are
relatively protected from the environment. Mutation has a significant
role to play in the origin of species or evolution
Historical Background
The earliest record of point mutations dates back to 1791, when Seth
Wright noticed a lamb with exceptionally short legs in his flock of
sheep. Visualising the economic significance of this short-legged
sheep. i.e., short legged sheep could not cross the low stone fence and
damage the crop fields in the vicinity, he produced a flock of sheep,
each of which having short legs by employing artificial breeding
techniques. The short legged breed of sheep was known
as Ancon breed. Later on, the trait of short legs was found to be

resulted from a recessive mutation and the short legged individuals

were found to be homozygous recessive
OCCURANCE
Mutations occur frequently in the nature and have been reported in
many organisms, e.g. Drosophila, mice and other rodents, rats, rabbits,
guinea pigs and man. In the Drosophila, mutation causes white and
pink eyes, black and yellow body colors, and vestigial wings. In
rodents the mutations are responsible for black, white and brown
coats. In man, the mutations cause variation in hair color, eye color,
skin pigmentation and several somatic malformations. Various
genetical diseases of human beings such as haemophila color
blindness, phenyl ketonuria, etc., form other examples of mutation in
human beings.
How does a mutation act?
Any change in sequence of nucleotides in the DNA will result in the
corresponding change in the nucleotide sequence of mRNA. This may
result in alignment of different tRNA molecules on mRNA (during
protein synthesis). Thus, the amino acid sequence, and, hence, the
structure and properties of the enzyme formed will be changed. This
defective enzyme or structural protein may adversely affect the trait
controlled by the protein. In consequence, a mutant phenotype makes
its expression.

MAHROSE NAWAZ -4155126

Classification on different criteria

According to size and quantity.

The DNA sequence of a gene can be altered in a number of ways.
Missense mutation
This type of mutation is a change in one DNA base pair that
results in the substitution of one amino acid for another in the
protein made by a gene.

Nonsense mutation
A nonsense mutation is also a change in one DNA base pair.
Instead of substituting one amino acid for another, however, the
altered DNA sequence prematurely signals the cell to stop
building a protein. This type of mutation results in a shortened
protein that may function improperly or not at all.

 Insertion
An insertion changes the number of DNA bases in a gene by
adding a piece of DNA. As a result, the protein made by the gene
may not function properly.

Deletion
A deletion changes the number of DNA bases by removing a piece
of DNA. Small deletions may remove one or a few base pairs
within a gene, while larger deletions can remove an entire gene or
several neighboring genes. The deleted DNA may alter the
function of the resulting protein(s).

 Duplication
A duplication consists of a piece of DNA that is abnormally copied
one or more times. This type of mutation may alter the function of
the resulting protein.

Frameshift mutation
This type of mutation occurs when the addition or loss of DNA
bases changes a gene's reading frame. A reading frame consists
of groups of 3 bases that each code for one amino acid. A

frameshift mutation shifts the grouping of these bases and

changes the code for amino acids. The resulting protein is usually
nonfunctional. Insertions, deletions, and duplications can all be
frameshift mutations.

Repeat expansion
Nucleotide repeats are short DNA sequences that are repeated a
number of times in a row. For example, a trinucleotide repeat is
made up of 3-base-pair sequences, and a tetranucleotide repeat
is made up of 4-base-pair sequences. A repeat expansion is a
mutation that increases the number of times that the short DNA
sequence is repeated. This type of mutation can cause the
resulting protein to function improperly.

According to origin:
Spontaneous mutation:
The spontaneous mutation occurs suddenly in the nature and
their origin is unknown. They are also called background
mutation and have been reported in many organisms such
maize ,bread molds ,microorganisms, mice and man etc.
Induced mutation:
besides naturally occurring spontaneous mutations , the
mutations can be induced artificially in the living organisms by
exposing them to abnormal environment such as radiation ,
certain physical conditions and chemicals. The substance or
agents which are induce artificial mutations are called
mutagenes or mutagenic agents.

FATIMA ASHRAF-415512

 According To Magnitude Of Phenotypic Effect

According to their phenotypic effects following kinds of
mutations may occur:
Dominant mutations:
The mutations which have dominant phenotypic expressions are called
dominant mutations. For example, in man the mutation disease
aniridia (absence of iris of eyes) occurs due to a dominant mutant
gene.

Recessive mutations:

Most types of mutations are recessive in

nature and so they are not expressed phenotypically immediately. The
phenotypic effects of mutations of a recessive gene is seen only after
one or more generations, when the mutant gene is able to recombine
with another similar recessive gene.

 Isoalleles:
Some mutations alter the phenotype of an organism
so slightly that they can be detected only by special techniques.
Mutant genes that give slightly modified phenotypes are called
isoalleles. They produce identical phenotypes in homozygous or
heterozygous combinations.

Lethal mutations:

According to their effects on the phenotype

mutations may be classified as lethal, subvitals and supervitals. Lethal
mutations result in the death of the cells or organisms in which they
occur. Subvitals mutations reduce the chance of survival of the
organism in which they occur. Supervital mutations, in contrast,
cause the improvement of biological fitness under certain conditions.
Temperature sensitive mutations or Ts mutations:
If
the substitution produces a protein that is active at one temperature
(typically 300C) and inactive at a higher temperature (usually 40-42 0C).
According to the Types of Chromosomes
According to the types of chromosomes, the mutations may be of following two
kinds:

Autosomal mutations:
This type of mutation occurs in
autosomal chromosomes. Examples include, Sickle Cell ( sickle shaped
blood cells), Tay Sachs Disease ( individuals cannot breakdown lipids in
the brain hence death at the age of 4) and many more.

Sex chromosomal mutations:

This type of mutation

occurs in sex chromosomes. Examples include Haemophilia, Color
Blindness, Male Pattern Baldness.

NOUSHEEN FATIMA-415511

Affect of Gene Mutation on Health

and Development of Human
In general, we all have two copies of each gene. We get one from each
parent. These genes actually code for various proteins. To function
correctly, each cell depends on thousands of proteins to do their jobs in
the right places at the right times. However, sometimes gene
mutations prevent one or more of these proteins from working
properly. By changing a genes instructions for making a protein, a
mutation can cause the protein to malfunction or to be missing entirely.

 Occurrence of mutations
In some cases, people are born with one, three, or more copies of
a particular gene. It is also possible for the gene to be entirely
missing.
A mistake could be made as DNA copies itself during cell division.
Somatic mutations occur in non-reproductive cells and won't be
passed onto offspring. For example, the golden color on half of
this Red apple was caused by a somatic mutation. Its seeds will
not carry the mutation.
Germ-line mutations are those that take place in the
reproductive cells and can be passed on to the
offspring.
Environmental factors such as ultraviolet radiation from the sun
can cause mutations as DNA copies itself during cell division.
Affect on Health
No affect:Most gene mutations have no impact on health or development. For
example, some mutations alter a gene's DNA sequence but do not
change the function of the protein made by the gene. This is because: Often gene mutations that could cause a genetic disorder are
repaired by certain enzymes before the gene is expressed and an
altered protein is produced. Each cell has a number of pathways
through which enzymes recognize and repair mistakes in DNA.
The mutation occurs in a stretch of DNA with no function. These
are called silent mutations.

Small change occurs in phenotype:A single mutation caused this cat's ears to curl backwards slightly.

Positive affect:A very small percentage of all mutations actually have a positive
effect. These mutations lead to new versions of proteins that help an
individual better adapt to changes in his or her environment. For
example, a beneficial mutation could result in a protein that protects
an individual and future generations from a new strain of bacteria.
Genetic disorders:When a mutation alters a protein that plays a critical role in the body,
it can disrupt the normal development or cause a medical condition

A condition caused by mutations in one or more genes is called a

genetic disorder.

Most inherited genetic diseases are recessive, which means that a

person must inherit two copies of the mutated gene to inherit a

disorder. This is one reason that marriage between close relatives is

discouraged; two genetically similar adults are more likely to give the
child two copies of a defective gene.
Some well-known inherited genetic disorders include cystic fibrosis,
sickle cell anemia, Tay-Sachs disease, phenylketonuria and
color-blindness. All of these disorders are caused by the
mutation of a single gene.
Cystic fibrosis
Cystic fibrosis (CF) is an autosomal recessive disease. It is
caused by mutations to the cystic fibrosis transmembrane
conductance regulator (CFTR) gene, located on human
chromosome 7. This leads to clogging of airways in the lungs and
interferes with pancreatic secretions of the enzymes that digest
proteins, carbohydrates, and fats in the small intestine.
Sickle cell anemia
Sickle cell disease is a group of disorders that affects hemoglobin, the
molecule in red blood cells that delivers oxygen to cells throughout the
body. It is caused by a mutation in a gene called hemoglobin
beta (HBB), located on chromosome 11.

Tay-Sachs disease
Tay-Sachs disease (TSD) is a fatal genetic disorder, most commonly
occurring in children. It results in the progressive destruction of the
nervous system. Tay-Sachs is caused by the absence of a vital enzyme

called hexosaminidase-A (Hex-A). This is due to defect in the gene that

codes for production of the enzyme Hex-A on chromosome 15.
Phenylketonuria
Phenylketonuria (PKU) is an inherited disorder of metabolism that
causes an increase in the blood of a chemical known as phenylalanine.
It leads to intellectual disability, behavioral problems, and mental
disorder. It is due to mutations in the PAH gene which results in low
levels of the enzyme phenylalanine hydroxylase. This enzyme is
responsible for converting phenylalanine to tyrosine.
Color-blindness
Color- blindness is usually a genetic (hereditary) condition. Red/green
and blue color blindness is usually passed down from parents. The
gene which is responsible for the condition is carried on the X
chromosome and this is the reason why many more men are affected
than women.
Affect on Development
In some cases, gene mutations are so severe that they prevent an
embryo from surviving until birth. These changes occur in genes that
are essential for development, and often disrupt the development of an
embryo in its earliest stages. Because these mutations have very
serious effects, they are incompatible with life.

FARWA ALTAF -415513

Mutation Rate

In genetics, mutation rate is a measure of the rate at which various

types of mutations occur over time.

Mutation rates are typically given for a specific class of mutation,for

instance point mutations,small or large scale insertions or
deletions.Mutation rates differ between species and between different
regions of the genome of a single species.These different rates of
nucleotide substitution are measured in substitutions(fixed
mutations)per base pair per generation
Mutation in intergenic or non coding DNA tend to accumulate at a
faster rate than mutations in DNA that is actively in use in the
organism(gene expression).That is not necessarily due to a higher
mutation rate but to lower levels of purifying selection.A region
which mutates at predictable rate is a candidate for use as a molecular
clock
If the rate of neutral mutations in a sequence is assumed to be
constant(clock-like)and if most differences between species are neutral
rather than adaptive, then the number of differences between two
different species can be used to estimate how long ago two species
diverged. In general, the mutation rate in unicellular eukaryotes and
bacteria is roughly 0.003 mutations per genome per cell generation.
Factores affecting the mutation rate:
Environmental stress

 UV light demage DNA

Applications of Mutation:
Human insulin gene was transferred into bacteria.The
genetically modified bacteria became able to synthesize
insulin.Diabetics are now receiving this insulin.
In 1977 an E.coli bacterium was created that was capable of
synthesizing the human growth hormone.
The hormone thymosin which may prove effective against
brain and lung cancer has been produced by genetically
modified microorganisms.
Beta-endorphin, a pain killer produced by the brain, has
also been produced by genetic engineering techniques.
Genetic engineers produced a safe vaccine against the foot
and mouth disease(a viral disease in cattle,goatsand deer)

 Interferons are anti- viral proteins produced by cells

infected with viruses.In 1980, interferon was produced in the
genetically modified micro organisms, for the first time.
The enzyme urokinase, which is used to dissolve blood
clots, has been produced by genetically modified
microorganisms.
Genetic engineers have developed plants that can fix
nitrogen directly from atmosphere.Such plant need less
fertilizers.
Genetic engineering techniques can also be used to cure
blood diseases like thalassemia and sickle-cell anaemia,
which result from defects in single genes.Normal genes could
be transferred into the bone marrow.

Significance of Mutation
Variability:
Mutations are the source of all variability in a
population.Variability inceases the adaptability of aorganism to its
environment and wards off death and deterioration in an
unfavouarble environment.
Study of genes:
Unless and untill a gene mutate and has a recessive or
intermediate allele, it will remain unnoticed and its importance in
the physiology and phenotype of the individual cannot be
evaluated.
Evolution:
Mutations are the foundation head of evolution.they add new
variations in the populations.The variations allow some organisms

to become better fitted in struggle of

existence.They,therefore,while others with less variations perish.
The process continues and the variations accumulate.It give rise
to new variaties,subspecies and species.Sometimes a single
mutation give to new type of organisms.Polyploidy has produced
a number of new organisms.It has been induced artificially to
obtain new species and better yield.

Industrial microbiology:
Workers are continuously developing newer mutant races of
microorganisms for better fermenting ability(e.g yeast),better
yield of antibiotics(e.g penicillium) and several other biochemicals
Health hazard:
Increasing use of mutagens exposes workers and other segments
of population to hazards of havind deleterious
mutations.Therefore,some countries have already imposed
restrictions and regulations on the use of mutagens.X-ray
technicians and workers in atomic energy plants are always
warned to extra careful towards incidental exposure.

 Animal Husbandry:
There are several varieties of domesticated animal and pets.All of
them have originated from wild types through mutations.Some
recent mutations include Ancon sheep,Hornless cattle,Hairless
cat, etc.Mutationa have also occurred for higher milk
yield,lactation period,egg production,meat contant,wool
yield,adaptability to diverse environments.These useful mutations
have been picked up by animal breeders.
Agriculture:
Mutations have played an almost revolutionary part in agriculture
both at the beginning of civilization as well as now in the
improvement of agriculture to meet the needs of ever-growing
human population
Plant breeders are using induced mutations for improvement
of crop plants for higher yield,nutritive value,stiffness of
straw,resistance to lodging,lesser duration of crop ripening,
disease resistance etc
The high yield called Reimer was produced through gamma
irradiation.
Reduction in the duration of crop plants without affecting
yield has been one of the important contributions of
mutation.Such mutations have been achieved in almost all
crops including sugarcane(18 months to less than 10
months), castor(9 months to 4.5 months, Aruna variety).
In vegetative propagated plants,mutations are the only
source of improvement and development of variability.The
induced mutations are somatic in nature.A somatic mutation
in banana has produced the variety Bhaskara. Seedless
Navel orange and seedless grapes are somatic
mutations.Somatic mutations have also helped improve
pineapple and potato.

 About 50% of the present day crop and horticultural plants

have developed in nature through polyploidy,e.g. Wheat,
Rice,Maiz, Cotton, Potato,Sugarcane,Banana,
Pineapple,Apple,Bear, etc

A large number of mutations have been induced in

ornamental plants in order to enhance their beauty,longer
life and fragrance,e.g, Dahlia, Rosa, Chrysanthemum.