DETAIL ABOUT MUTATION
1)Defination:-dna & structure
3)Cause of mutation
4)Types of mutation:-
a)effect of germ line mutation
6)Sickle cell disease & Trait
7)Role of Bioinformatics
What is DNA?
DNA or deoxyribonucleic acid is the hereditary
material in humans and almost all other
organisms. Nearly every cell in a person’s body
has the same DNA. Most DNA is located in the
cell nucleus (where it is called nuclear DNA), but
a small amount of DNA can also be found in the
mitochondria (where it is calledmitochondrial
DNA or mtDNA).
DNA is made of a long sequence of smaller
units strung together. There are four basic types of
unit: A, T, G, and C. These letters represents the
type of base each unit carries: adenine, thymine,
guanine, and cytosine. The sequence of these
bases encodes instructions. Some parts of your
DNA are control centers for turning genes on and
off, some parts have no function, and some parts
have a function that we don't understand yet.
Other parts of DNA are genes that carry the
instructions for making proteins — which are long
chains of amino acids. These proteins help build a
Protein-coding DNA can be divided into codons— sets
of three bases that specify an amino acid or signal the
end of the protein. Codons are identified by the bases
that make them up — in the example at right, GCA,
for guanine, cytosine, and adenine. The cellular
machinery uses these instructions to assemble a
string of corresponding amino acids (one amino acid
for each three bases) that form a protein. The amino
acid that corresponds to "GCA" is called alanine; there
are twenty different amino acids synthesized this way
in humans. "Stop" codons signify the end of the newly
After the protein is built based on the sequence of
bases in the gene, the completed protein is released
to do its job in the cell.
WHAT IS MUTATION
A mutation is a change in DNA, the hereditary material of life. An
organism's DNA affects how it looks, how it behaves, and its
physiology. So a change in an organism's DNA can cause changes in all
aspects of its life.
Mutations are essential to evolution;
they are the raw material of genetic
variation. Without mutation,
evolution could not occur.
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). Such a substitution could:change a
codon to one that encodes a different amino
acid and cause a small change in the protein
produced. For example,sickle cell anemia is
caused by a substitution in the beta-
hemoglobin gene, which alters a single
amino acid in the protein produced.
change a codon to one that encodes the
same amino acid and causes no change in
the protein produced. These are called silent
change an amino-acid-coding codon to a
single "stop" codon and cause an incomplete
protein. This can have serious effects since
the incomplete protein probably won't
Insertions are mutations in
which extra base pairs are
inserted into a new place
in the DNA.
Deletions are mutations in
which a section of DNA is
lost, or deleted.
• 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. These changes are called
frameshifts.For example, consider the
sentence, "The fat cat sat." Each word
represents a codon. If we delete the first letter
and parse the sentence in the same way, it
doesn't make sense.
• In frameshifts, a similar error occurs at the DNA
level, causing the codons to be parsed
incorrectly. This usually generates truncated
proteins that are as useless as "hef atc ats at" is
• There are other types of mutations as well, but
this short list should give you an idea of the
Chromosome segment breaks off
Segment flips around backwards
Occurs when a gene sequence is
• Involves two chromosomes that aren’t homologous.
• Part of one chromosome is transferred to another
The causes of mutations
1. DNA fails to copy accurately:-
Most of the mutations that we think matter to evolution
are "naturally-occurring." For example, when a cell
divides, it makes a copy of its DNA — and sometimes the
copy is not quite perfect. That small difference from the
original DNA sequence is a mutation.
2. External influences can create mutations:-
Mutations can also be caused by exposure to specific chemicals or
radiation. These agents cause the DNA to break down. This is not
necessarily unnatural — even in the most isolated and pristine
environments, DNA breaks down. Nevertheless, when the cell repairs
the DNA, it might not do a perfect job of the repair. So the cell would
end up with DNA slightly different than the original DNA and hence,
Since all cells in our body contain DNA, there
Are lots of places for mutations to occur
However , some mutations cannot be passed
on to offspring and do not matter for
Somatic mutations occur in non-reproductive
cells and won't be passed onto offspring. For
example, the golden color on half of this Red
Delicious apple was caused by a somatic
mutation. Its seeds will not carry the
2)Germ line mutation:-
The only mutations that matter to large-scale
evolution are those that can be passed on to
offspring. These occur in reproductive cells like
eggs and sperm and are called germ line
Effects of germ line mutations
1. No change occurs in phenotype
2. Small change occurs in phenotype
3. Big change occurs in phenotype
1)No change occurs in phenotype.
Some mutations don't have any noticeable effect on the
phenotype of an organism. This can happen in many
situations: perhaps the mutation occurs in a stretch of DNA
with no function, or perhaps the mutation occurs in a protein-
coding region, but ends up not affecting the amino
acid sequence of the protein.
2) Small change occurs in phenotype.
A single mutation caused this cat's ears to curl
3)Big change occurs in phenotype.
Some really important phenotypic changes, like DDT resistance
in insects are sometimes caused by single mutations. A single
mutation can also have strong negative effects for the organism.
Mutations that cause the death of an organism are called lethals-
and it doesn't get more negative than that.
Little mutations with big effects: Mutations to control genes
Mutations are often the victims of bad press — unfairly stereotyped as unimportant or as a
cause of genetic disease. While many mutations do indeed have small or negative effects,
another sort of mutation gets less airtime. Mutations to control genes can have major
(and sometimes positive) effects.
Some regions of DNA control other genes, determining when and where other genes are turned
"on". Mutations in these parts of the genome can substantially change the way the organism is
built. The difference between a mutation to a control gene and a mutation to a less powerful
gene is a bit like the difference between whispering an instruction to the trumpet player in an
orchestra versus whispering it to the orchestra's conductor. The impact of changing the
conductor's behavior is much bigger and more coordinated than changing the behavior of an
individual orchestra member. Similarly, a mutation in a gene "conductor" can cause a cascade of
effects in the behavior of genes under its control.
Many organisms have powerful control genes that determine how the body is laid out.
Example- Hox genes are found in many animals (including flies and humans) and designate
where the head goes and which regions of the body grow appendages. Such master control
genes help direct the building of body "units," such as segments, limbs, and eyes. So evolving a
major change in basic body layout may not be so unlikely; it may simply require a
change in a Hox gene and the favor of natural selection.
Mutations to control genes can transform one body part into
flies carrying Hox mutations that sprout legs on their
foreheads instead of antennae!
A case study of the effects of mutation: Sickle cell anemia
Sickle cell anemia is a genetic disease with severe symptoms, including pain and
anemia. The disease is caused by a mutated version of the gene that helps make
hemoglobin —a protein that carries oxygen in red blood cells. People with two copies
of the sickle cell gene have the disease. People who carry only one copy of the sickle
cell gene do not have the disease, but may pass the gene on to their children.
How Does a Child Get Sickle Cell DIsease?
• Sickle cell disease is inherited through genes. Genes contain messages that
are passed on to the child through the mother's egg and the father's sperm.
These messages control such qualities as eye color, blood type, and the kind
of hemoglobin a person will have, etc.
• Germs do not cause sickle cell disease and you cannot catch it from another
person like you catch a cold.
• For a child to have any form of sickling disease, each parent will have an
abnormal hemoglobin. One possibility is that each parent has sickle cell trait
(AS). Another possibility is when one parent has the disease (SS) and the
other parent has sickle cell trait (AS).
• In hemoglobin SC disease, one parent has sickle cell trait and the other
parent has a different trait (hemoglobin C). In sickle beta-thalassemia, one
parent has sickle cell trait (or sickle cell anemia) and the other parent
carries the trait for beta thalassemia (or has thalassemia major).
Where the mutation occur in Anemia
Official Gene Symbol: HBB
Name of Gene Product: hemoglobin, beta
Alternate Name of Gene Product: beta globin
Locus: 11p15.5 - The HBB gene is found in region 15.5 on the short (p) arm
of human chromosome 11.
sickle-cell anemia is caused by a single point mutation in the nucleotide sequence of β-globin.
The mutation is located in the seventh codon (The first codon codes for Met, the leader amino
acid in polypeptides). The seventh triplet should read GAG which colds for glutamic acid, but
the middle nucleotide has changed to a thymine,
which changes the triplet to GTG, which codes for valine.
Replacement of the normally charged glutamic acid
with the hydrophobic valine.
Replacement of the normally charged glutamic acid
with the hydrophobic valine alters the solubility of hemoglobin, so that at a lower oxygen
concentration, the altered protein changes the red blood cell to a sickle shape
that is unable to carry oxygen. This causes the symptoms of sickle-cell anemia.
There are effects at the protein level
Normal hemoglobin (left) and
hemoglobin in sickled red blood
cells (right) look different; the
mutation in the DNA slightly
changes the shape of the
hemoglobin molecule, allowing it
to clump together.
Protein Function: Hemoglobin molecules, which
reside in red blood cells, are responsible for
carrying oxygen from the lungs to various parts of
the body for use in respiration. The HBB gene
codes for one of the two types of polypeptide
chains found in adult hemoglobin. Normal adult
hemoglobin is a tetrameric protein consisting of two
alpha chains and two beta chains. HBB codes for the
beta chain, which is often referred to as beta globin.
Mutant beta globin is responsible for the sickling of
red blood cells seen in sickle cell anemia
There are effects at the cellular level
>Normal red blood cells are round,
soft, and flexible. Since they can
squeeze through small blood
vessels, blood flows easily.
>When red blood cells are shaped
like a sickle, they are hard and
rigid. These sickled cells can get
stuck and plug up small blood
vessels. The flow of blood and
oxygen can be slowed down or
How to get β-globin sequence
A. Focus on-actual nucleotide sequence for the β-
B. This sequence was obtained from GeneBank.
C. KEY WORD: HUMHBB
D. There are actually 73,308 nucleotides for
hemoglobin, which is located at the tip of
Chromosome 11. This includes the β-globin gene
as well as several other related globin genes .
E. The sequence that contains the β -globin
information is located between nucleotides
62,137 → 63,660.
There are 1,473 nucleotides in the gene, enough to code for 491 triplet codons. But
the β-globin polypeptide has just 146 amino acids.The excess nucleotides are “introns”
(intervening sequences) that separate the protein coding "exons“ (expressed
sequences). The β-globin gene consists of three exons and two introns.
Exon #1 62187 – 62278
Intron #1 62279 – 62409
Exon #2 62410 – 62631
Intron #2 62632 – 63481
Exon #3 62482 – 63610
Type- NCBI goto EMBL-EBI
Sequence Translation is used to translate nucleic acid sequence to
corresponding peptide sequences.
1)Transeq (EMBOSS):-EMBOSS Transeq translates nucleic acid
sequences to the corresponding peptide sequences.
2) Sixpack (EMBOSS):-EMBOSS Sixpack displays DNA sequences
with 6-frame translation and ORFs.
Back-translation is used to predict the possible nucleic acid sequence
that a specified peptide sequence has originated from.
1) Backtranseq (EMBOSS):-EMBOSS Backtranseq back-translates
protein sequences to nucleotide sequences.
2) Backtranambig (EMBOSS):-EMBOSS Backtranambig back-
translates protein sequences to ambiguous nucleotide sequences.
A particular slide catching your eye?
Clipping is a handy way to collect important slides you want to go back to later.