Mutations, types , causes

1. Mutations
Definition
Mutation is basically alteration of one or more nucleotides in an organism extra chromosomal DNA, virus or any
material related to gene.
Explanation
Mutation is permanent change .It may vary in size from genome to genome.This alteration may be of single
nucleotide or in a large fragment containing more than one gene or multiple gene.Mutation is the only cause of
dissimilarities between individuals of same species and different one .Mutation may lead to evolution .
Historical background
Dr Young Seok Ju said "This is the first time that anyone has seen where mutations arise in the very early human
development. It is like finding a needle in a haystack. There are just a handful of these mutations, compared with millions
of inherited genetic variations, and finding them allowed us to track what happened during embryogenesis."
Dr Inigo Martincorena from the Sanger Institute, said: "Having identified the mutations, we were able to use
statistical analysis to better understand cell dynamics during embryo development. We determined the relative
contribution of the first embryonic cells to the adult blood cell pool and found one dominant cell -- that led to 70 percent
of the blood cells -- and one minor cell. We also sequenced normal lymph and breast cells, and the results suggested that
the dominant cell also contributes to these other tissues at a similar level. This opens an unprecedented window into the
earliest stages of human development."
Prof Sir Mike Stratton said "This is a significant step forward in widening the range of biological insights that
can be extracted using genome sequences and mutations. Essentially, the mutations are archaeological traces of embryonic
development left in our adult tissues, so if we can find and interpret them, we can understand human embryology better.
This is just one early insight into human development, with hopefully many more to come in the future."
Causes
DNA fails to copy accurately
Most mutation is naturally occurring .when cell devide it makes makes copy of DNA Some time copy not perfect.
Small difference from original DNA is mutation.
External influences can create mutations
Mutation can cause by specific chemicals or radiations. These cause to break DNA. When cell repair the DNA then it
might not be a perfect job.
Type
Substitution
It is a mutation that exchanges one base for another.
Insertion
In which extra base pair are inserted into a new place of the DNA.
Deletion
The type of mutation in which a section of DNA is lost or deleted.

2. Frameshift
Protein coding DNA is divided into codons three bases long insertions and deletions can alter a gene that its
message is no longer correctly parsed. These changes are called frameshifts.
Gene mutation:
Genes are piece of DNA and collection of nucleotides form a DNA .Gene mutation is describe as any change in the
nucleotides sequence which sequence make the DNA. This change occur in single nucleotide base or large segment
of many nucleotide sequence. During transcription DNA is converted into RNA and then translation start and form the
proteins. Due to changing in nucleotide sequences form nonfunctioning proteins. Genetic variations come due to
mutational changes in genetic code which promote to diseases.
Types:
There are some basics types of gene mutation.
Point mutation:
Point mutations is the simple type of gene mutation. In which type of mutation single base pair altered at one point. It
mostly proceed during DNA replication .In single nucleotide change can alter the complete sequence of DNA. There
are different mutagens which produce mutation. Mutagens can be UV rays ,chemicals, X-rays ,high temperature etc.
T A A C T G C A G
Point mutation
T A A C C G C A G
Point mutation classified into following types:
1-Silent Mutation
2-Missense Mutation
3-Nonsense Mutation
Silent Mutation:
In which single nucleotide change but new genetic codon can encode for same amino acid. A set of three nucleotide
coded for amino acid. It has no effect on protein function.
For example CGT, CGC, CGA, and CGG coded for arginine. If the arginine sequence altered CGC to CGA, then also
arginine will formed.
Alternation of this type in nucleotide called synonymous change, both the old and new codon code for the same amino
acid.
Missense Mutation:
In which type of mutation sequence of nucleotide change various amino acid are formed. Different types of protein are
formed. It may be harmful or valuable. This type of change is a non-synonymous change.
For example, if the CGC converted into GGC, glycine will be formed at the place of arginine.
Nonsense Mutation:
In which mutation amino acid codon changes into a stop codon. This type of change brings non sense codon (UAA,
UAG, UGA) at a new position due to this change protein synthesis stop.
Insertion:
In this type of mutation one or more nucleotide base pair are added into a sequence of DNA.It is mostly caused by
jumping genes or replication process when errors occur. Protein made by gene that is not perform proper function.
Deletion:
In which segment of DNA is removed which consist of one or more nucleotide.

3. C C A A C T C G A
INSERTION
C C
G A A C T C G A
DELETION
( T )
C C G A A C C G A
Frameshift mutation
Frame shift is a type of gene mutations in which number of nucleotide added or delete and not produce a three codon
base pair sequence and produce incorrect product of translation. Some they may be responsible for producing stop
codon during translation.
Every three base have produce own specific product any deletion or addition of cause the alteration of amino acid
product. Frame shift mutations is dangerous. Frame shift mutation may be useful or valuable i.e. may be lethal product
may be change into the useful product. For example in cause of bacteria we can introduce a frame shift mutation to
produce nylonase enzyme which can degrade nylone.
Frame shift mutation divided into two types:
Deletion
Insertion
Example of frameshift mutations
Tay-sachs diseases
Some types of cancer
Crohn’s disease

4. Cystic fibrosis
HIV
Hypertrophic cardiomyopathy
Tay sach’s disease:
Tay-sachs disease is a fetal disease which is commonly infect the fetues and small children’s. there is no treatment
available for the tay-sachs disease. Mutations cause in HEX A gene with 78 types of mutations in which 65 are
dangerous and cause lethal effect. Frame shift mutations lead to the early stop codon involve in disease.
Chrmosome Mutation
A change in chromosome is known as chromosomal mutation . any change in the structure or sequence of the
chromosome is reffered as mutation. As well as structure is altered, the mutation change the number of cells. The
mutations involve deletion duplication inversion and translocation. Chromosomal structures are usually large in size
and contains hereditary material that is DNA . chromosomes are present in the nucleus of our cells. Gene mutation
change the single gene but chromosomal mutation can change the whole chromosome
Types Of chromosomalMutation
Deletion:
Deletion is the lost of the nucleotides from the chromosomes the lose could be in larger number or in smaller number.
Deletion is actually when a base is deleted from the sequence. Chromosomal fragment are lost due to deletion of a
base. There is no specific location for deletion, it can happens anywhere or everywhere.
As shown in the figure . some part or a single base or gene is removed or deleted from the sequence of the
chromosome. From this sequence( A B C D E F) , the (B) is deleted or lost. This deletion is known as chromosomal
deletion.
Sometimes the one copy of gene is lost from the organism which have two copies before or sometimes both the copies

5. from an organism lost.
Duplication :
Duplication is opposite to deletion. In deletion a part is lost and in duplication a part is copied or replicated. A
sequence is repeated or may be a single base or two bases are repeated or duplicated. So it means that the this type of
chromosome have an extra information or repeated information. The double in the fragments of the chromosome Is
resulted in duplication. The duplication of the hereditary material. Due to chromosomal duplication the new hereditary
or genetic material occurs. It is also responsible for many types of errors. “Common sources of gene duplications
include ectopic recombination, retro transposition event, aneuploidy, polyploidy, and replication slippage”
As shown in the figure1 that is shown above (in deletion) . Fro the sequence (A B C D E F) the B is duplicated (A B B
C D E F) . this duplication is known as chromosomnal replication or chromosomal duplication.
Mechanismof Duplication :
There are following five mechanism of duplication that are defined below,
Ectopic recombination :
Duplication due to unequal crossing over occurs during meiosis in misaligned homologous chromosomes. It occurs
due to the replication of two elements of chromosome .
ReplicationSlippage :
It is actually a error in the DNA . due to which short sequences are repeated in the chromosomes. DNA polymerases
starts copiyng the DNA during replication process.it place the Strand in wrong location and accidently copy the strand
again due to which the duplication occurs. Replication slippage is actually the repetitive sequences
Retrotransposition:
If viral proteins aberrantly attach to cellular mRNA,they can reverse transcribe copies of genes to create retrogenes.
“Retrogenes usually lack intronic sequences,and often contain poly A sequences that are also integrated into the
genome. Many retrogenes display changes in gene regulation in comparison to their parental gene sequences,which
sometimes results in novel functions.”
Aneuploidy
“Aneuploidy occurs when non disjunction at a single chromosome results in an abnormal number of chromosomes.
Aneuploidy is often harmful and in mammals regularly leads to spontaneous abortions (miscarriages). Some aneuploid
individuals are viable, for example trisomy 21 in humans, which leads to Down syndrome. Aneuploidy often alters
gene dosage in ways that are detrimental to the organism; therefore, it is unlikely to spread through populations.”
Harmful Mutation:
mutation occurs in DNA or in genes or sometimes in chromosomes. We know that in mutation some part
are missing or some part is duplicated. If some part is missing then proper proteins is not produced then our
body not able to perform a proper function. So disease occurs.
In all of us body, mutation are present. And these mutations are inherited from parents. If mutation
transferred from parents then its mean mutation present in our germ line. Other types of mutation are also
present like due to environment or radiations etc. some mutations are beneficial but others are harmful. Some
common like cystic fibrosis, sickle cell anemia, Tay-sachs disease etc. These are due to mutation of single
gene. Most diseases that are inherited are recessive. Its mean that when both copies are carrier then disease

6. occur otherwise not. So marriage between cousins is not good. Because if close relations or cousins are
married then child have both copies of defective gene. so disease easily appeared.
Some types of disease are due to one copy of defective gene like Huntington’s disease. But this is very rare.
Scientist estimated that in every person, 5 to 10 genes are mutated. But diseases are not occurring because
one copy of bad gene is not able to produced disease.
Cancer:
it is due to mutation in single gene. A gene named p53 is cause cancer. p53 gene that used for cell cycle and
tumor suppression. But due to mutation in p53, the ability of tumor suppression is inactive and not able to
produced proteins that regulate cell cycle. So tumor produced.
Sickle Cell:
This is due to point mutation. Mean only one nucleotide mutation in hemoglobin is the reason of sickle cell
disease. And red blood cells have sickle cell shape due to mutation. These sickle cell red blood cells block
the capillaries. But for sickle cell disease, it is necessary that two copies of mutated genes are present. Single
copy of gene not able to produced sickle cell disease.
Progeria:
Genetic disorder and commonly called Hutchinson-Gilford Progeria, causes accelerated aging. Children who
suffered from this disease are died commonly at the age of 13. And some at the age of 20. Death due to heart
attack. This disease is due to the mutation in LAMNA gene. this gene is used to make a proteins that have
the ability to support cell nucleus.
Proteus Syndrome:
In this, our bone are extra grow. Sign and symptoms appeared after 6 to 18 months of birth. Present 1 in one
million people. And severity rate is varying. This disease is due to the mutation in AKT1 gene. This gene
used is cell growth.
Huntington’s disease:
In this disease, people have lost the ability of think and talk. This disease is due to mutation in chromosome
number 4(HD gene). In this disease, basal ganglia cells are destroyed. These cells controlled emotions and
movement. This disease has 50% chance to pass to the next generation. Symptoms appear between 30 to 50
ages.
Severe Combine Immuno DeficiencySyndrome:
Very rare disease. This is due to mutation in SCIDX1 gene. This gene present on X chromosome. This gene makes a
protein that make IL2RG receptor.
Beneficial Mutation
Beneficial mutations are the mutations which has positive effects. These are basically variations occur in
genome during course of natural selection. These types of mutation can be obtained throughout in the normal
population or organisms of community. Beneficial mutations are found in all type of organisms.
1) Beneficial Mutations in Humans
The beneficial mutations are the mutations which brings evolutionary changes. These may arise from
environmental factors and adaptation and response to these factors. Some of the examples are given as
below.
a.Apolipoprotein AL Milano
b.Increased bone density
c. Malaria resistance
d. Tetrachromatic vision

7. a) Apo lipoprotein
All humans have a gene which are said to be apolipoprotein. The function of this gene is to transport
cholesterol via the process of bloodstream. It is considered more beneficially due to the removal of cholestrol
from arteries.
Apo lipoproteins are antioxidants that are used to prevent from swallowing. People have a gene named as
PCSK9 that cause low expression of heart disease.
b) Increased bone density
The gene which caused bone density in human being are said to be low lipoprotein related to protein 5
(LRP5).
This variation occurs in a young person of Midwest family in car crash. Due to this crash the person bone not
is break. X RAY analysis shows that the person belongs to those families which have stronger bones than
average.
c) Malaria resistance
These variations occur in humans due to the hemoglobin variation that make it like sickle shape. When one
copy present it cause the disease like malaria resistance but when there are two copies present it caused the
disease like sickle cell anemia that is not actually by this mutation. The missing of one copy of that gene in
human causes 29% chances to get malaria. On the other hand people with two copies of this gene respond to
93% of that disease.
d) Tetra chromatic vision
Different genes present in humans shows different color vision of light. The gene which has one kind of cone
show blue color at chromosome at 7.The other two kinds shows the effect of both red and green on the X
chromosome.
2) Beneficial mutation in organisms
Mutation that occurs in organism are said to be somatic or germ line. Germ line mutations are those
mutations that are tans formed from parents to offspring through reproduction cells. Due to the long term
effect of this mutation it is considered as the beneficial mutation. The examples of beneficial mutation in
organism are as follow.
a) Nylonase: nylon bacteria
Nylonase are the most authentic example of beneficial mutation in bacteria. Nylonase eat the short molecule
of nylon 6.Mutation occur in that bacteria due to the insertion of single nucleotide in genetic material. This
mutation was found in 1940 due to the presence of nylon.
b) Gene mutation: Almond Trees
The species which have almond contain amygdalin. Amygdalin is a chemical that convert the cyanide into
human body. A single gene mutation in this type of almond trees shows that there is no long production of
amygladin.
c) Murry Gray: A Breed of Beef Cattle
Murry gray are known as cattle bread which can be obtained from cow species. In this case the specific cow
produced more productive calves than others. Soon after the differences were identified and breed with
positive characters were produced which ultimately became popular in all regions of Australia.
References
https://www.google.com.pk/?gws_rd=cr&ei=ZgvnWOelD4HyUOu9uJAB#q=mutation
https://www.google.com.pk/?gws_rd=cr&ei=ZgvnWOelD4HyUOu9uJAB#q=mutation+history
https://www.google.com.pk/?gws_rd=cr&ei=ZgvnWOelD4HyUOu9uJAB#q=mutation+causes
https://www.google.com.pk/?gws_rd=cr&ei=ZgvnWOelD4HyUOu9uJAB#q=mutation+types
http://www.biotechnologyforums.com

8. https://www.thoughtco.com/gene-mutation-373289
https://ghr.nlm.nih.gov/primer/mutationsanddisorders/possiblemutations
http://evolution.berkeley.edu/evolibrary/article/mutations_03
https://ghr.nlm.nih.gov/primer/mutationsanddisorders/genemutation
https://en.wikipedia.org/wiki/Mutation
https://www.reference.com/science/four-types-chromosomal-mutations-40fd109602a4f912
https://www.reference.com/science/four-types-frameshift-mutations-40fd109602a4f912