Gene Expression and Genetics

Mutation
Mutation is a permanent change in the DNA of an organism.

Difference between Germ-line mutations and Somatic mutations

Somatic mutations

Mutations that occur in the somatic cells either during development or in adulthood will not be
inherited by the next generation.

Germ-line mutations

mutation is present in the gametes and passed on the offspring, all the cells in that individual
will carry the mutation.
Types of Mutations based on the outcome

The mutations can be classified into three types based on their outcome:

• Silent mutation

Any change in the sequence of DNA, which has no further impact on the amino acid
sequence in a protein or in the functions performed by a protein. There is no
phenotypic indicator of mutation.

• Nonsense mutation

Due to a point mutation (gene mutation) there is change in the sequence of base pair
leading to stop codon. It results in a shortened or non-functional protein.

• Missense mutation

As a result of point mutation (gene mutation) leading to change of base in the codon,
which then codes for another amino acid.

Mutagens and types of mutagens

A mutagen is defined as any physical, chemical or biological substance that can change the
genetic material of an organism, thereby causing a mutation.

Mutations can occur due to natural and artificial reasons.

1. Mutations due to artificial factors

When the DNA is exposed to certain chemicals or radiations, it causes the DNA to
break down.
• Physical mutagens: These include ionizing radiation, such as X-rays, gamma rays
and alpha particles. ultraviolet radiations cause the thymine dimers to break resulting
in a mutated DNA.
• Chemical mutagens: Elements such as arsenic, nickel and chromium are considered
to be mutagens. Some organic compounds like benzene are also considered to be
mutagenic in nature.
• Biological mutagens: Examples of biological mutagens involve transposons and
viruses. Furthermore, certain bacteria such as Helicobacter pylori can increase the
risk of developing stomach cancer.
 2. Mutations due to natural factors
During DNA replication mistakes may occur and can cause mutations.

Types of mutations

There are three types of mutations.

1. Gene Mutations (Point mutation)

2. Chromosomal Mutations
3. Whole-chromosome mutations

Gene Mutations (Point mutation)

Change in the structure of DNA / Change of one, or a small number of nucleotides. These
usually take place during DNA replication, and their consequences can be benign, or can be
devastating.

Point mutations occur through,

a. Insertion
An insertion occurs when an extra nucleotide is incorporated into the DNA sequence
during replication. It can be a repetition of one of the bases already there or a different
base entirely.
 b. Substitution
Substitution refers to the case in which one nucleotide is incorrectly swapped during
DNA replication for another nucleotide, meaning the correct nucleotide is replaced with
an alternative nucleotide.
This type of mutation only affects one codon. However, this does not mean the resulting
effects will be small.

c. Deletion
Where a base is completely lost from the sequence

Insertions and deletion mutations are often considered more harmful than substitutions,
because they impact upon the way the rest of the sequence is read by the cell.
Consequences of Point mutations and examples
1. Missense mutations
Missense mutations occur due to point mutations and it usually caused by
substitutions. Even though only one amino acid is affected, the consequences can be
deleterious.

Eg: Sickle Cell Anemia

2. Nonsense mutations

Nonsense mutations are a special kind of missense mutation where the amino acid
change results in the production of a stop codon (TAG, TAA or TGA).

This premature stop codon results in the production of a truncated protein, which is
usually non-functional.

Eg: Duchenne muscular dystrophy

 3. Frameshift mutations
Insertions and deletions of nucleotides can result a frameshift mutation. If an additional
1 or 2 nucleotides are added or removed, the sequence is ‘shifted’.

(When an extra letter (J) is inserted, the whole sentence loses its meaning)
Eg: Tay-Sach’s disease

Chromosomal Mutations
Involve changes in the positions of whole genes within the chromosomes.
These mutations are larger scale mutations than point mutations, typically involving segments
of entire chromosomes.

1. Deletion
Chromosomal deletions involve the loss of an entire region of a chromosome and all the
genes contained within it.
 Eg: Cri du Chat Syndrome.

(deletion in chromosome 5. It is a rare genetic disorder, and the name comes from the
French for “cat-like cry”, which refers to the unusual kitten-like cries of affected
children).

2. Inversion

Chromosomal inversions occur when a particular sequence is flipped and reinserted,

meaning the sequence is in the opposite orientation. This does not typically cause
disease.

3. Duplication
Chromosomal duplications involve the repetition of a region of the chromosome,
resulting in double the number of genes (and gene products).
4. Translocation
Chromosomal translocations occur when a part of one chromosome is incorrectly fused
to a segment of another chromosome. The danger of these types of mutations is the
possibility for gene fusions.

Eg: Philadelphia chromosome (chronic myeloid leukaemia)

The Philadelphia chromosome is an example of a translocation, where two segments of

chromosome 9 and chromosome 22 swap places. This results in a gene fusion that
encodes a hybrid protein that is always ‘on’, meaning it is overactive. This contributes
to cancer by allowing the cell to divide uncontrollably.
Whole-chromosome mutations
The loss or duplication of a whole chromosome
Eg: Down syndrome is caused by a whole-chromosome mutation at chromosome 21,
individuals with this syndrome have three copies of this chromosome instead of the usual two

How Gene Mutations Can Affect the Phenotype

Most mutations are neutral, which means that they neither improve nor worsen the chances of
survival. Some mutations cause much damage, disrupting the biochemistry of the whole
organism.

If a harmful mutation is in a protein that is important to the function of a cell.

Example, the active site of an enzyme - the effect can be catastrophic

Reasons for most mutations will have no observable effects on the organism
1.If the mutations occur in part of the non-coding DNA which does not affect the way the
genetic code is read.

2. If the code is degenerate, and one small change in the code may not alter the amino acid
coded for the protein.
Sickle cell disease
Sickle cell disease is a genetic disease that affects the protein chains of the haemoglobin in the
red blood cells. It is the result of a point mutation.

A change of one base in one codon changes a single amino acid in a chain of 147 amino acids
but that change alters the nature of the protein.

As a result, the haemoglobin molecules stick together to form rigid rods that give the red blood
cells a sickle shape.

They do not carry oxygen efficiently and can prevent the blood flowing in the capillaries.
 How a change in a single nucleotide
can affect the structure and function of the protein formed

Genetics: The Basis of Inheritance

Genetics is a branch of biology concerned with the study of genes, genetic variation, and
heredity in organisms.

Gregor Mendel, a scientist and Augustinian friar working in the 19th century, was the first to
study genetics scientifically.

Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to
offspring.
Key Terms used in Genetics
Phenotype
The physical and chemical characteristics that make up the appearance of an organism are
known as its phenotype.

Genotype
The genotype is the part of the genetic makeup of a cell
The genotype is expressed when the information encoded in the genes' DNA is used to make
protein molecules.

The expression of the genotype contributes to the individual's observable traits, called the
phenotype.
 Reasons for variation in genotype between individuals of a species
1. Rearrangement of genes during meiosis

Independent assortment

Crossing over
2. Inheritance of genes from two different individuals in sexual reproduction.

Fertilization of gametes is a completely a random process.

Homologous Chromosomes / Homologous pairs

The cells of every individual organism within a species contain the same number of
chromosomes.

Half the chromosomes are inherited from the female parent and the other half come from the
male parent.

The two sets can be arranged as matching pairs, called homologous pairs
Locus
The chromosomes in a homologous pair carry the same genes except for the sex chromosomes.
The gene for any particular characteristic is always found in the same position or locus.

Alleles
Each gene exists in slightly different versions called alleles. For example, at the locus for the
gen.

Homozygous ('the same')

If both alleles that code for a particular characteristic are identical, then the individual is
homozygous for that characteristic.
Heterozygous ('different')

If the two alleles coding for a characteristic are different, the individual is heterozygous

for that characteristic and is called a heterozygote.

Dominant

Some phenotypes are dominant: their effect is always expressed whether the individual is
homozygous or heterozygous for the allele.

If one allele for the dominant phenotype is present it will be expressed even if an allele for the
recessive allele present.

The alleles coding for dominant phenotypes are usually represented by a capital letter.
Recessive
Phenotypes of certain alleles are not expressed to outside. These alleles are known as recessive
alleles. Recessive phenotypes are shown by lower- case version of the same letter.
True breeding / Pure bred
True breed is a kind of breeding wherein the parents would produce offspring that would carry
the same phenotype. This means that the parents are homozygous for every trait.

If we cross two individuals that are homozygous for the same characteristic, all the offspring
of all the generations that follow will show this same characteristic in their phenotype (unless
a mutation occurs).

Monohybrid Crosses
If genes are considered individually in a genetic cross, it is called as a monohybrid cross.

We can represent these crosses using simple diagrams called Punnett squares.

A Punnett square shows the potential alleles inherited from both parents, and the potential
offspring that results.

Garden Pea Plant (Pisum sativum)

Also known as common pea / garden or field pea

It is a herbaceous plant which usually self-pollinated. Diploid (2n=14 chromosomes).

Opposite Characteristics of Garden Pea Plant

Cross between a pea plant homozygous for the dominant round pea seed shape and a
pea plant homozygous for the recessive wrinkled pea
Test Cross

Whether the individual is homo- or heterozygous is unable to determine from outside.

Therefore, to find it out,

the individual must be crossed with a homozygous recessive individual. This type of cross,
known as a test cross, and it reveals the parental genotype.
Codominance

Codominance is a form of inheritance wherein the alleles of a gene pair in a heterozygote are
fully expressed.

Neither allele can mask the expression of the other allele.

As a result, the phenotype of the offspring is a combination of the phenotype of the parents.
Thus, the trait is neither dominant nor recessive.

Example:

Determination of Human blood group

In the human ABO blood group system there are three possible alleles

A, B and O

These are usually shown as

IA, IB and IO

The different alleles code for the presence or absence of antigens on the surface of the
erythrocytes.

• IO codes for no antigens

• IA codes for antigen: A
• IB codes for antigen: B

IA and IB are codominant. This means both alleles are expressed and produce their proteins,
which act together without mixing.

So, an individual who inherits IA and IB will have both antigen A and antigen B on the surface
of their erythrocytes and they will have the blood group AB.

Blood Group Genotypes

A IA IA IA IO
B IB IB IB IO
AB IA IB
O IO
Predicting children’s blood groups of Parents having Blood group A and O

Predicting children’s blood groups of Parents having Blood group B and O